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Gary G Schwartz, PhD, MD, PhD; David Schmitz, MD; Marilyn Klug, PhD
Title: Radon Testing via the North Dakota Tobacco Quitline
Abstract:
Purpose: Tobacco quitlines are found in all 50 US states and offer services like counseling,
nicotine gum, and drugs to callers interested in quitting smoking. Radon is an invisible,
odorless, tasteless, radioactive gas that accumulates in basements and is the leading
source of residential exposure to ionizing radiation. Quitlines represent an opportunity
to reach a population at elevated risk from radon gas. Radon is the 2nd leading cause
of lung cancer (after smoking) and smokers exposed to lung cancer have a ten times
greater risk of developing lung cancer.
Methods: North Dakota has high indoor radon due to high levels of uranium in the soil and
cold winters. Two-thirds of homes in North Dakota have high radon, above the 4 pCi/L
cutoff that the EPA recommends for remediation. Many houses may also exceed 20 pCi/L.
Therefore, we worked with the ND QuitLine to provide radon information and services.
Callers were offered a free radon test kit. We also measured demographics, interest
in test kits, and test kit return rate.
Results: Over the course of 500 callers, 251 (50%) requested a kit and 75 (15%) sent it in
for testing. We found that among callers, only 20% knew radon caused lung cancer.
And for returned test kits, half had radon levels that exceeded 4 pCi/L.
Conclusion: Our feasibility study found that radon education and test distribution via a tobacco
quitlin
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Sydney Rea; Soojung Kim, PhD, MPH
Title: Radon Testing: Remember, it’s important!
Abstract:
Purpose: This feasibility study tests the effectiveness of smartphone calendar reminders to
increasing the borrowing and use of digital radon test detectors at Grand Forks Public
Library. In collaboration with the library, downloadable calendar links will be promoted
via its digital newsletter, website, and social media over three months. By leveraging
existing resources with minimal investment, this study could offer a scalable strategy
to improve radon testing.
Methods: We will provide a downloadable calendar invite that prompts participants to test their
homes for radon after checking out a digital test kit from the Grand Forks Public
Library, featuring recurring reminders at various times and dates with the library
as the meeting location. This link will be promoted over three months via the library’s
website, digital newsletters, and social media platforms. To assess the intervention’s
effectiveness, we will compare checkout rates of the digital radon test kits before
and after the calendar reminders are implemented.
Anticipated Results: Since April 2023, the Grand Forks Public Library's digital radon detector program
has averaged a monthly circulation of 43 tests without waitlists. Outcomes include:
(1) behavioral: monthly circulation and waitlist numbers, (2) analytical: click-through
rates from promotional channels, and (3) qualitative: patron interviews.
Conclusion: If smartphone calendar reminders prove feasible for increasing radon testing, we
can evaluate their effectiveness through clinical trials, develop tailored strategies
based on geographic and lifestyle differences, and recommend this cost-effective approach
to public health organizations to boost home radon testing rates.
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Mark R Williamson, PhD
Title: Small-Scale Radon Reduction Experiments
Abstract:
Introduction: Radon is a radioactive gas and residential risk factor for lung cancer. While radon
remediation is straightforward, the current gold-standard—active ventilation—can be
expensive and involve extensive structural modification. Therefore, my future research
goal is to construct high-radon sheds to test alterative radon remediation devices
that are 1) low-cost, 2) flexible, and 3) efficient. To provide proof-of-concept data
to support that research project, I have set up miniature radon chambers.
Methodology: I constructed four small acrylic radon chambers using granite chunks as radon emitters
and continuous monitors for measuring radon. Each experimental run tested radon levels
before and after treatment. Across experiments, I tested air circulation, Spanish
moss, and activated charcoal. At the end of each experiment, the data was extracted
from the radon monitors and analyzed, controlling for chamber variability.
Results: In Experiment 1, a combination of Spanish moss and an active fan significantly reduced
radon. Conversely, in Experiment 2, neither Spanish moss treatment provided significant
radon reduction, while activated charcoal did. In Experiment 3, activated charcoal
significantly reduced radon levels with or without an active fan, consistent across
two set replicates. For Experiment 4, while activated charcoal reduced radon, there
was no evidence of a dose response, at least for volumes with the same exposed surface
area.
Conclusions and Significance: The acrylic test chambers have proven to be a stable and cost-effective method of
running tests with radon, building a body of experimental evidence that will assist
with future scaled-up experiments for radon reduction.
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Abdullah Reda; Jonathan Cortese; Sherief Ghozy; Aryan Gajjar; Dani Douri; Ramanathan
Kadirvel; David F. Kallmes
Title: Can the clot meniscus and claw signs predict thrombectomy and clinical outcomes
in patients with stroke? A systematic review and meta- analysis
Abstract:
The angiographic shape of an occlusion, like the clot meniscus sign and the claw sign,
has been reported to potentially impact the recanalization rate and clinical outcome
in patients undergoing mechanical thrombectomy for acute ischemic strokes. Following
PRISMA guidelines, a systematic literature search was conducted across PubMed, Scopus,
Embase and Web of Science databases. Patients were grouped into clot meniscus/claw
sign positive and negative groups based on the definitions obtained from each study.
Primary outcomes included technical success, with a meta- analysis performed using
a random- effects model to calculate proportions and odds ratios (OR) with 95% confidence
intervals (Cl). We included seven studies recruiting 1572 patients. The results indicated
that the positive and negative groups had comparable first- pass effect (OR 1.95;
95% CI 0.76 to 5.01; P=0.167) and final recanalization (OR 1.36; 95% CI 0.81 to 2.27;
P=0.248) rates. However, the rate of having a favorable functional outcome was significantly
higher in the positive group than in the negative sign group (OR 1.91; 95% CI 1.25
to 2.92; P<0.003). Within the sign- positive population, the use of contact aspiration
was associated with a significantly higher rate of recanalization compared with using
a stent retriever (OR 0.18; 95% CI 0.07 to 0.49; P<0.001). This result did not translate
into a clinical impact, as both stent retriever and contact aspiration showed comparable
rates of functional independence at 3 months (OR 0.22; 95% CI 0.02 to 2.33; P=0.210).
The presence of the clot meniscus/claw sign is not associated with recanalization
outcomes after thrombectomy. However, it might be a good sign to predict which thrombectomy
technique might be associated with better recanalization, although current evidence
may need further confirmation.
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Madhur Shetty; Chris R. Brown; Gary G. Schwartz, PhD, MPH, PhD; Marilyn G. Klug, PhD;
James D. Foster, PhD
Title: Impact of Lead exposure on Dopamine Transporter Function: Potential link between
Environmental Toxicology and Parkinson’s Disease
Abstract:
Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder marked
by the loss of dopaminergic (DAergic) neurons and dopamine (DA) dysregulation. Although
most PD cases are idiopathic, emerging epidemiological evidence suggests that environmental
factors, including lead (Pb²⁺) exposure, may play a significant role in disease etiology.
Recent studies have linked lead (Pb²⁺) in drinking water, mobilized by acid rain,
and the presence of municipal lead service lines, with increased PD prevalence. However,
the molecular mechanisms underlying this association remain unclear.
Our study focuses on the dopamine transporter (DAT), a presynaptic protein critical
for clearing extracellular dopamine (DA) and maintaining DAergic tone. Dysregulation
of DAT function contributes to neuropsychiatric conditions including depression, PD,
ADHD, schizophrenia, and substance use disorders. Using a translational framework,
we examined whether Pb²⁺ exposure in the drinking water of rats or in an immortalized
DAergic cell line (N27) affects DAT activity, expression, and post-translational regulation
via phosphorylation and palmitoylation.
ur findings show that a 30-day exposure to 1000 ppm Pb²⁺ in drinking water reduced
DA uptake capacity without altering total DAT expression in rat striatal synaptosomes.
A decrease in DA transport capacity was also seen in N27 cells exposed to relatively
low concentrations (300-500 μM or 63-105 ppm) without significant cellular toxicity.
In contrast to animals, reduced DA transport was accompanied by a decrease in total
cellular DAT in cells but without any change in cell surface DAT expression. While
palmitoylation of DAT was unaffected, phosphorylation at Thr53 trended upward in response
to Pb²⁺ in both synaptosomes and neuronal cells.These results indicate that Pb²⁺ disrupts
DAT function independent of surface expression or palmitoylation, with an upward trend
in Thr53 phosphorylation potentially serving as a compensatory mechanism in order
to maintain cell surface levels of DAT in response to overall decreased levels of
cellular DAT. These findings suggest that reduced DA uptake efficiency offers a mechanistic
link between environmental lead exposure and DAergic dysfunction in PD.
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Anupom Deb Nath; Estelle Leclerc, PhD; Stefan Vetter, PhD
Title: Identification of Ligand-Specific Monoclonal Anti-RAGE Antibodies Using a Live-Cell
NanoLuciferase Assay
Abstract:
Purpose: The receptor for advanced glycation end products (RAGE) is a cell surface receptor
that has functions on normal physiology and got upregulated in diseased conditions
such as diabetes and cancer. The full-length RAGE protein comprises a variable-like
(V) domain, constant type 1 (C1) and constant type 2 (C2) domains, a transmembrane
segment, and a cytoplasmic tail. RAGE has multiple ligands such as AGEs, HMGB1, S100
proteins, amyloid β peptides etc. Targeting RAGE to block specific ligand interactions
holds therapeutic potential across multiple diseases. This study aims to identify
ligand-specific RAGE antagonists using a live-cell system.
Methods: The NanoLuciferase complementation system, NanoBiT, was utilized to investigate RAGE-ligand
interactions. For this purpose, HEK293 cells were stably transfected with an LgBiT-tagged
human RAGE (hRAGE) receptor. To complement the LgBiT, SmBiT-tagged S100B and HMGB1
were employed, as both ligands are known to bind RAGE. Following complementation of
LgBiT and SmBiT, luciferase activity was measured upon the addition of furimazine
substrate. Changes in luminescence signals were assessed to identify ligand displacement
by anti-RAGE antibody binding.
Results: A stable cell line expressing the target receptor (LgbiT_hRAGE) was generated and
characterized. SmBiT-tagged S100B and HMGB1 proteins were successfully constructed,
expressed, and purified. The interaction between LgBiT_hRAGE and SmBiT-tagged proteins
effectively reconstituted the NanoLuciferase enzyme. Furthermore, the NanoBiT system
demonstrated the ability to detect competition with untagged S100B, and detected antibodies
demonstrating specific RAGE-ligand interactions.
Conclusion: This system successfully identified ligand-specific receptor antagonists, paving the
way for further characterization of receptor antagonists for therapeutic purposes.
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Yousuf Alam, MS; Estelle Leclerc, PhD
Title: Effect of RAGE inhibition on vemurafenib treatment in BRAF mutated melanoma
tumors
Abstract:
Purpose: BRAF mutations are present in over half of melanoma tumors, making vemurafenib a targeted
treatment option for these patients. However, resistance to vemurafenib often develops
within seven months during the treatment. The receptor for advanced glycation (RAGE)
plays a critical role in melanoma progression by modulating cell proliferation, and
tumor cell survival through the inhibition of apoptosis, and modulation of different
signaling pathways regulated by PI3/AKT, STAT3, and SAPK/JNK. Moreover, RAGE has been
implicated in therapy resistance through regulation of autophagy. We hypothesize that
RAGE inhibition enhances the sensitivity of melanoma cells to vemurafenib by decreasing
cell proliferation, modulating autophagy and the signaling pathway regulated by PI3/AKT,
STAT3, and SAPK/JNK.
Method: We investigated the synergistic effects of vemurafenib in combination with the RAGE
inhibitor FPS-ZM1 in the WM115 human melanoma cell line. Cell viability was assessed
using Alamar Blue, and drug synergy was analyzed using the Combenefit software. Changes
in the levels of the autophagic markers LC3-I/-II and p62, the signaling pathways
regulators SAPK/JNK, PI3/AKT and STAT3 are currently being evaluated by western blot
analysis.
Results: Our data suggest that RAGE inhibition sensitize BRAF mutated melanoma cells to vemurafenib,
and we observed the strongest synergistic effects with 30μM vemurafenib and 10μM FPS-ZM1.
Our initial Western blot results suggest that the drug combination reduces the autophagic
flux.
Conclusion: Our findings suggest that RAGE inhibition sensitizes BRAF mutated melanoma cells to
vemurafenib.
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Benjamin Roche, PhD
Title: Characterizing conserved G0 maintenance mechanisms to fight dormant cancers
Abstract:
Cancer research is making tremendous progress—yet a key challenge remains: the persistence
of minimal residual disease after primary tumor treatment, resulting in relapse and
secondary tumors with significantly worse phenotypes, prognosis and chemoresistance.
Multiple mechanisms contribute to persistence, in particular equilibrium with the
immune system and the phenomenon of tumor dormancy.
Dormant cancer cells, although rare, disseminate early to distant organs. Their exit
from the cell cycle to a G0 phase (cellular quiescence) shields such cells from chemotherapy,
which primarily relies on drugs targeting actively-dividing cells (such as DNA replication
poisons), as well as from the immune system. Re-entry of G0 cells into the cell cycle
results in tumor relapse and metastasis after months to years of sub-clinical disease,
and these cancer cells can benefit from years of accumulated mutations conferring
them further resistance to treatments. How can we address the fundamental need to
find strategies to target dormant cancer cells and prevent tumor relapse?
Studies across eukaryotic evolution over the past decade have shown that G0 is an
actively-maintained cellular state. Furthermore, our lab discovered that specific—and
conserved—molecular pathways are required for cell viability specifically in model
dormant cells, particularly involving RNA metabolism. This strongly suggests that
there are dormancy-specific oncogene addictions in cancer cells, and is uncovering
a panel of novel therapeutic targets to be used in combination with traditional approaches.
As current drug screening protocols, both in vitro and pre-clinical studies, are not
designed to identify drugs specifically active on dormant cancer cells, we are developing
new assays with model eukaryotes to not only delineate the full range of targetable
G0 pathways, but also start the first high-throughput screens to identify G0-active
drugs. We aim to synergize this research with translational labs and approaches, to
discover and test anti-dormancy cancer drugs.
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Gavin Salisbury; Sarmad Al-Marsoummi, PhD; Seema Somji, PhD; Donald Sens, PhD; Scott
Garrett PhD
Title: Investigation of the Effect of Cell Surface Marker CD133 in Renal Progenitor Cells
Abstract:
The proximal tubule of the kidney is the main site of damage after exposure to toxins,
hypoxia, or major injury. The renal tubular progenitor cell population is responsible
for the recovery and regeneration of the proximal tubule after these events. These
renal progenitor cells are sparsely scattered within the kidney and identified by
their co-expression of the known stem cell markers CD133 and CD24. The hypothesis
of this study is that CD133 plays a critical functional role in stemness and self-renewal
of renal progenitor cells. Using CD24+/CD133+ renal progenitor (HRTPT) cells isolated
from the immortalized RPTEC/TERT1 proximal tubular cell line, we established a CD133
knockdown with a lentiviral vector expressing short hairpin against CD133. We assessed
gene and protein expression of CD133 and select stem cell markers using RT-qPCR and
Simple Western procedures. We measured self-renewal capability by nephrosphere formation
under ultralow-attachment conditions and multipotent differentiation capacity by cell
growth under adipogenic, tubulogenic, osteogenic, and neurogenic conditions. Results
showed that CD133 knockdown in HRTPT cells caused a significant decrease in the expression
of stem cell markers (CD133, OCT4, SOX2, KLF4, CD44, and CMYC) and reduced self-renewal
capacity as indicated by reduced nephrosphere formation. In addition, CD133 knockdown
significantly decreased the differentiation capacity in tubulogenic and osteogenic
media.
Our results indicate that CD133 is critical for stem/progenitor characteristics in
HRTPT cells and loss of CD133 results in decreased ability to perform self-renewal
and multipotent differentiation capacity, indicating the importance of CD133 as a
potential therapeutic target in acute kidney injury.
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Jordan Giewat; Sarmad Al-Marsoummi, PhD; Donald Sens, PhD; Scott Garrett, PhD
Title: Attenuation of Cisplatin-induced toxicity and effect upon cell cycle arrest in renal
proximal tubular cells via Canagliflozin, an SGLT2 Inhibitor
Abstract:
Cisplatin is a commonly effective chemotherapeutic, yet acute kidney injury is a significant
dose-limiting factor in cisplatin-based therapies. Canagliflozin (INVOKANA®), an SGLT2
inhibitor, has demonstrated off-target renoprotection against cisplatin, though it
is poorly understood. It is necessary to investigate this phenomenon by utilizing
an in-vitro proximal tubule model to determine the protective effect of canagliflozin
in cisplatin-exposed proximal tubule cells. RPTEC/TERT1 is a commercially available
immortalized cell line from human cortical cultures with proximal tubule-like features,
from which we isolated HRTPT and HREC24T populations, with stem-like features and
more differentiation, respectively. We hypothesize that canagliflozin treatment to
cisplatin-exposed RPTEC/TERT1 cells will decrease cisplatin-induced toxicity and effect
cycle arrest previously observed in HRTPT cells. RPTEC/TERT1 cells were treated with
clinically relevant canagliflozin doses and exposed to moderately toxic cisplatin
levels for 48 and 72 hours to assess concentration and time-dependency of canagliflozin
on cisplatin toxicity, followed by crystal violet staining to determine cell viability,
and HRTPT cell culture in cisplatin- treated and canagliflozin-treated media to investigate
the prevention of cell cycle arrest. Our results indicate that canagliflozin has a
significant effect on cisplatin toxicity. Cell viability in canagliflozin-treated
RPTEC/TERT1 cells improved in a concentration dependent manner, and canagliflozin
attenuated cell cycle arrest in HRTPT cells. In conclusion, this suggests canagliflozin
attenuates cisplatin toxicity in human proximal tubule cells at clinically relevant
concentrations and cisplatin-induced cell cycle arrest in HRTPT cells. Moving forward,
we will continue to investigate cisplatin-induced cell cycle arrest, and how canagliflozin
influences gene expression in cisplatin-exposed proximal tubule cells.
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Sunisha Tangpong; Fardad Azarmi, PhD
Title: Antibacterial Thermal Spray Coatings: The Future of High-Efficiency Sterilization
in Biomedical Applications
Abstract:
Infection through surface transmission of bacteria is an ongoing concern surrounding
the spread of disease. As bacteria accumulates on surfaces, biofilm forms as clusters
of bacteria that are encased by a protective matrix. In the medical industry, mitigation
of biofilm is a particularly difficult challenge due to its antimicrobial resistance
characteristics, thus allowing infection to persist. Several medical interventions
are currently used to treat device and tools-related infections, including long-term
anti-microbial strategies and combinations of antibiotics and surgical revision. Unfortunately,
these interventions carry the risk of re-infection, often at higher rates, and the
development of antibiotic resistance. In this study, we try to avoid the formation
of biofilms by deposition of metallic alloy coatings that exhibit naturally-occurring
antimicrobial properties onto desired surfaces such as surgical instruments, tools,
and containers. Thermal spray coating technology available at Hard Coating Research
Laboratory (HCRL) at North Dakota State University is used for deposition of a well-known
biocompatible metallic alloy “Ti-6Al-4V”. The deposited coatings not only protect
surfaces against corrosion and wear but are also capable of releasing ions when in
contact with microbes and germs. To this end, several coupon samples are prepared
by culturing certain types of bacteria on coated and uncoated surfaces. The number
of remaining bacteria after allotted time on each surface is counted to evaluate the
capabilities of the surfaces in elimination of germs and bacteria. This method will
reduce the need for excessive use of antibacterial agents and sterilizing materials
before, during, and after every medical procedure.
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Christianah Jemiyo; Brett A. McGregor; Hasin Rehana; Junguk Hur, PhD
Title: Racial and Geographic Disparities in the Health Impact of Adverse Childhood Experiences:
Evidence from 33 U.S. States
Abstract:
Introduction: Adverse Childhood Experiences (ACEs) have been linked to a wide range of chronic health
conditions in U.S. adults. While this connection is well documented, there’s still
a pressing need to understand how these associations play out across different racial
and ethnic groups. Early life adversity, coupled with structural inequities, may compound
health risks in historically marginalized populations. This study investigates the
relationship between ACE exposure and chronic disease, with a particular focus on
racial disparities and geographic patterns across the United States.
Methodology: We used data from the Behavioral Risk Factor Surveillance System (BRFSS), spanning
33 states from 2019 to 2023. ACE scores were categorized into none, low (1–2), and
high (3 or more). We applied log-binomial regression to examine associations between
ACE scores and 17 health outcomes, adjusting for age, sex, race/ethnicity, income,
and education. Subgroup analyses were conducted by race/ethnicity, and state-level
patterns were summarized.
Results: Among 359,507 respondents, 24.4% reported high ACE exposure. The most common ACEs
were emotional abuse, parental separation, and living with someone who had a substance
abuse problem. Individuals with high ACE scores had an increased risk of depression,
smoking, coronary heart disease, and several other chronic conditions. Subgroup analysis
revealed notable racial disparities: while white respondents with high ACE scores
were significantly associated with many outcomes, American Indian and Alaska Native
(AIAN) respondents showed the highest risk ratios for heart attack, coronary heart
disease, and stroke. State-level analysis showed that ACE prevalence and related health
burdens varied across the country, with Oregon and Nevada reporting the highest mean
ACE scores.
Conclusion and Significance: High ACE exposure is consistently linked with poor health outcomes, but these impacts
are not evenly distributed. Racial and geographic disparities point to the need for
more targeted public health interventions. Efforts to prevent and address ACEs should
be responsive to the lived experiences of different communities and take into account
the broader social and policy contexts that shape the prevalence and impact of ACEs
within these communities.
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Michael Hill; Sarah Johnson; Sara Faraji Jalal Apostal, PhD; Sergei Nechaev, PhD;
Damien Parrello, PhD
Title: UND Genomics Core: Sequencing Excellence and Analysis Empowerment
Abstract:
The University of North Dakota (UND) Genomics Core provides a large panel of sequencing
services, along with an innovative cloud-based bioinformatics platform.
The UND Genomics Core offers a diverse set of sequencing technologies from Nanopore,
Illumina, 10X Genomics, and NanoString. Leveraging these technologies, the Core provides
various sequencing services including bulk, single-cell, or spatial RNA-seq, methylation
analysis, targeted and whole genome sequencing.
Understanding the growing need of the great majority of biologists to independently
analyze genomics data, the UND Genomics Core has developed an innovative bioinformatics
platform, GenomEX. GenomEX provides fully personalized (adjustable CPU/GPU numbers
& memory/storage capacity), dedicated (resources available 24/7 without any queue)
and customizable (users have administrator rights) cloud-based high-performance computing
environments. It enables biologists to seamlessly install over 13,000 bioinformatics
tools, generate and execute custom code or command lines, and receive real-time guidance
from an AI-based bioinformatics assistant—all through intuitive, one-click processes.
Overall, the UND Genomics Core is a center of excellence where state-of-the-art technologies
and cutting-edge ideas converge to advance the field of genomics.
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