bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Cigarette Smoke Induced Oxidative DNA Damage of Wild Type & XPC Knockdown Human Bronchial Cells Using Human 8-oxoguanine DNA Glycosylase 1
Authors: Campbell Jarrett , Zhou Huaxin , Sears Catherine 
Published: January 2019

Background and Hypothesis:
Chronic exposure to cigarette smoke (CS) induces DNA lesions and oxidative damage leading to the development of lung diseases such as emphysema and lung cancer. Xeroderma Pigmentosum group C (XPC) is a protein which repairs CS bulky DNA lesions and oxidative DNA damage, including 8-OHdG. We hypothesize that in vitro CS exposure will result in increased 8-OhdG and that XPC knockdown (KD) leads to higher levels of 8-OHdG.
Experimental Methods:
Briefly, immortalized normal human bronchial epithelial cells (Beas2B), were cultured and subsequently exposed to CS extract to induce DNA damage. Cells in agarose were then gently lysed, immersed in an alkaline buffer, incubated with hOGG1 enzyme, and analyzed for DNA damage using single cell electrophoresis (Comet Assay). Slides were stained and viewed by fluorescence microscopy. DNA damage is expressed as tail moment, measured by CometScore. Statistical analysis was performed using 2-way ANOVA (SigmaStat) with p-value < 0.05 indicating statistical significance.
Results and Conclusion:
Both XPC KD and wild-type (WT) Beas2B cells treated with 2.5% CS measured higher levels of DNA damage than air control. The addition of hOGG1 lead to an increase in the tail moment in both AC and CS-exposed cells, indicating an increase in the oxidative DNA lesion, 8-OHdG. Finally, XPC KD exposed to 2.5% CS demonstrated an increase in DNA damage and in 8-OHdG compared to WT (p<0.001). In conclusion, these results further support that CS leads to increased oxidative DNA damage and suggests a role for XPC in regulation and repair of the oxidative DNA lesion, 8-OHdG.
Evaluating the effect of a Participatory Music Program on the Quality of Life and Community Reintegration of Homeless Veterans in Indianapolis
Authors: Cheng Phillip , Myers Laura , Lillie Aimee , Myers Jennifer , Crow Shannon , Rattray Nick , Wasmuth Sally , Hook Brittany , Lustig Ann , Burns Deb , Bravata Dawn 
Published: January 2019

Background:
Among Veterans, homelessness is a well-recognized, major problem. Approximately 20% of homeless persons in Indianapolis are Veterans. The Domiciliary Care for Homeless Veterans Program provides residential care for housing insecure Veterans with multiple needs. However, difficulty in combating issues of isolation and lack of avocation for members of the Program remains. Our goal and belief is that providing veterans with a participatory arts will significantly improve their quality of life and reintegration into the community.
Methods:
This prospective study will use mixed methods to compare intervention participants with usual care controls. Veterans will complete standardized measures including the 20-Item Short Form Health Survey, for quality of life, and Flow State Scale-2, for level of program engagement. Veterans who transition to community housing will complete the Military to Civilian Questionnaire. Veterans will also participate in semi-structured interviews for qualitative data.
Anticipated Results:
We anticipate that quality of life will improve among homeless Veterans who participate in the study compared to usual care controls. Further, that we will observe a higher level of community reintegration for participants who leave the Domiciliary.
Significance:
Offering an intervention that looks to change how Veterans see themselves in specific social roles and change how they structure their lives is vital in tackling issues contributing to homelessness.
Potential Impact:
This project will provide preliminary data about a participatory music program regarding improvement in quality of life for Veterans with housing insecurity. Findings can be used to build a larger implementation trial across VA domiciliaries nation-wide.
Establishing a Comprehensive Ethics-Based Checklist for Surgical Camp Activities at AMPATH-Kenya
Authors: Choi, BS Diane B. , Carpenter, MD Kyle L. , Keung, MD Connie H. 
Published: January 2019

Background and Hypothesis: Global health has made strides in controlling and reducing harm from infectious diseases such as Polio and HIV/AIDS but this focus has not been mirrored in surgical and anesthesia care, especially in many low and middle-income countries (LMICs). In 2010, an estimated 16.9 million lives were lost from conditions that required surgical care and 5 billion people in LMICs lack safe and affordable surgical and anesthesia. Organization of surgical camps can bring skilled physicians to temporarily meet the unmet surgical needs in underserved areas. However, currently there are no government agencies or accrediting bodies existing to assess the scope/impact of short-term surgical camp care or establish standards of care for such services.
Experimental Design or Project Methods: The AMPATH mission of “start with healthcare and then do more to empower communities, educate tomorrow’s medical experts and research breakthroughs that will truly change the health of the world” was incorporated into the ethical checklist proposed. The four principles – beneficence, non-maleficence, autonomy, and justice were used as guidance for the checklist.
Results: The checklist can be organized into three main areas: Care, Empowerment & Training, and Research (Figure 1).
Role of CaMKK2 in Osteocytes within the Bone Microenvironment
Authors: Clough Nick , Williams Justin , Sankar Uma 
Published: January 2019

Background and Hypothesis:
The Ca+2/calmodulin (CaM)-mediated protein kinase kinase 2 (CaMKK2) is a multi-functional kinase with effects on cell proliferation, differentiation and metabolism. The role of CaMKK2 in bone has been explored with its ablation favoring osteoblasts to osteoclasts and bone mass accrual as observed in Camkk2-/- mice, or following its inhibition by STO-609. One outstanding question is whether the anabolic effects of CaMKK2 are bone-cell intrinsic. While analyzing mice harboring bone-cell specific deletion of CaMKK2, we observed a high bone mass phenotype when the kinase is deleted from osteocytes, the most abundant cells within the bone. We therefore hypothesized that the loss of CaMKK2 enhances osteocyte differentiation.
Experimental Design or Project Methods:
We used two osteocyte cell lines MLO-Y4 and MLO-A5, both generated from mice expressing the immortalizing T-antigen, to test our hypothesis. The MLO-A5 line has post-osteoblast/pre-osteocyte characteristics while the MLO-Y4 line has mature osteocyte characteristics. CaMKK2 expression was silenced in MLO-A5 cells using Lentiviruses encoding CaMKK2 short hairpin (sh) RNA constructs. STO-609 was employed to inhibit CaMKK2 in the MLO-Y4 line as it proved resistant to transfection. Immunoblotting was used to verify CaMKK2 silencing/inhibition. Comparisons on cell morphologies were observed using immunofluorescence. As osteocytes are defined by dendritic morphology, the number of dendritic processes were analyzed. Additionally, the differences in the expression of the osteocyte markers SOST, E11 and DMP1 were examined by qRT-PCR.
Results:
To be finalized.
Conclusion and Potential Impact:
Overall, our studies will provide more information towards understanding the role of CaMKK2 in bone biology and aid its development as a therapeutic target in the treatment of osteoporosis.
Humble But Powerful: The Role of “Access to Information & Knowledge” in Implementation Success in the RE-INSPIRE Study
Authors: Fry, M.S. Colin M. E. , Miech, PhD Edward J. 
Published: January 2019

Background and Hypothesis:
This study examines the role access to information and knowledge in acute stroke care following a 2011 stroke quality improvement clustered randomized trial and a national acute ischemic stroke (AIS) directive in the Veterans Health Administration. Access to information is associated with the highest levels of acute stroke care provision, as well as other key organizational features.
Experimental Design or Project Methods:
A multidisciplinary team analyzed and conducted semistructured interviews of clinical providers across 11 VAMCs over a 3-year period. The interviews were then coded and analyzed using a mix methods approach. This study focused on the “Access to Information and Knowledge” organization feature defined in the Consolidated Framework for Implementation Research constructs.
Results:
The manifestations of this organizational feature include: stroke binders, intranet share-points, pocket cards, algorithms, checklists, templates, stroke kits, flow sheets, care maps, posters, and room signs. Acute stroke is a low-volume, high stakes, time sensitive condition at these sites. Therefore, proper access to information is especially important to ensure a continuity of care that transcends the idiosyncrasies of individual providers allowing for quick, correct, and complete care of the patient.
Conclusion and Potential Impact:
The mere presence of certain tools in a clinical setting is not enough, but rather the feature relies on getting the right information, to the right people, at the right time. Access to information exemplifies the need for implementation science, and insights from this study can be broadly applied to a plethora of scenarios in other clinical settings.
Effect of Frataxin Knockout on Mouse Cardiomyocytes Using DsRed.T3 as a Quantifying Marker
Authors: Galante Eric , Pride P Melanie , Chen, MD Frances , Payne, MD R Mark 
Published: January 2019

Background and Hypothesis:
Discosoma Red (DsRed) is a strong fluorescent marker that has many practical uses for scientific studies. We engineered a transgenic mouse expressing DsRed.T3 only in cardiomyocyte nuclei, and then crossed this with a conditional knockout mouse with loss of Frataxin (FXN) in heart. It is known that dysfunction of the Frataxin (FXN) gene can cause Friedrich’s Ataxia (FRDA), a disease associated with ataxia, weakness and dilated cardiomyopathy in humans. The current study aimed to: 1) Determine if DsRed overexpression in cardiomyocyte nuclei would negatively affect cardiac tissue, and 2) Use the DsRed.T3 mouse to determine whether FXN knockout (KO) would cause a loss of cardiomyocytes.

Experimental Design or Project Methods:
The study was done by examining three different strains of mice: wild-type, DsRed.T.3 overexpressing Tg mice, and FXN KO mice with loss of FXN in cardiomyocytes. Mice were analyzed using genotyping, frozen immunofluorescent stains, α-actinin and Hoechst, TPLSM, confocal microscopy, western blotting, H&E, echocardiography, and heart:body weight ratios.
Results:
Results showed that DsRed.T3 localized to the nucleus of cardiomyocytes and that after 6.5 months there were some significant effects on cardiac function, although not on cardiac tissue. Further analysis is ongoing to determine if there is a loss of cardiomyocytes within the FXN KO group.
Conclusion and Potential Impact:
This study shows promise for how researchers can study the heart, and more specifically, Friedreich’s Ataxia, while also shedding light on how FXN may ultimately affect the heart in FRDA patients.
Is Liver Function Homogenous? Correlation between CT Liver Volumes and Liver Function as Determined by Functional Hepatobiliary (HIDA) Scan
Authors: Gary, MS Jarrell G. , Haste, MD Paul , Tann, MD Mark 
Published: January 2019

Background
A hepatobiliary (HIDA) scan is a study historically done to evaluate for cholecystitis and more recently shown to be an effective way to measure liver function. Volumetric analysis on computed tomography (CT) is the most common way to evaluate future liver remnant prior to planned partial hepatectomy or radiation therapy. The aim of this study is to determine to what degree do lobar CT volume ratios correlate with distribution of functionality.
Experimental Design
A retrospective review and analysis of the images for 63 patients with liver cancer, imaged between 2016 and 2018, was performed. All functional HIDA scans were processed using MIM software. Total liver function, with lobar ratios, were obtained. Whole liver and lobar volume analysis on CT was also performed.
Results
The mean age was 63.6 [Symbol] 11.0 years with a male to female ratio of 1.3:1. The mean total liver volume on CT was 1611.3 [Symbol] 590.5 mL (Right lobe: 961.5 [Symbol] 405.3 mL, Left lobe: 649.8 [Symbol] 331.7 mL). The mean ratio of right to left lobar volumes was 59.5 [Symbol] 13.5 % to 40.6 [Symbol] 13.5%. The mean ratio of right to left lobar liver function was 60.7 [Symbol] 20.7% to 39.5 [Symbol] 21.1%.
Conclusion and Potential Impact
The overall average ratio between right and left lobe liver function appears to closely relate to the volumetric ratio between the lobes. These promising results suggest that liver function is fairly homogenous, which could provide great value in planning future liver operations and radiation therapy.
Blueberry containing diets protect from bone loss induced by sex steroid deficiency differently depending on sex and by mechanisms independent of canonical sex steroid receptor signaling
Authors: Johnson O R , Sato A Y , Pellegrini G G , Cregor M , McAndrews K , Atkinson E , Choi R B , Maiz M , McCabe L D , McCabe G P , Peacock M , Weaver C M , Burr D , Bellido T 
Published: January 2019

Background and Hypothesis:
There is an unmet need for interventions that prevent bone loss induced by sex steroid deficiency. Loss of estrogens or androgens increases ROS in bone. We hypothesized that diets containing blueberries with antioxidant properties would protect from bone loss induced by sex steroid deficiency, depending on sex and on the expression of Nrf2, a transcription factor that regulates the endogenous antioxidant response.
Experimental Design:
SHAM, ovariectomized (OVX), or orchidectomized (ORX) 4-month-old, wild type (WT) or Nrf2 knockout (KO) male and female mice were fed with control diet or diets containing 3 types of blueberries. Bone mineral density (BMD) and bone microarchitecture were measured by dual-energy x-ray absorptiometry and microscopic computed tomography, respectively; and gene expression was quantified in bone RNA by quantitative PCR.
Results:
Control-fed OVX or ORX mice exhibited the expected BMD loss, to a similar extent, in WT and KO mice. One of the blueberry diets (Montgomery) prevented bone loss, totally in females and partially in males; and prevented ~50% of microarchitecture deterioration in ORX mice, independently of Nrf2 expression. OVX and ORX decreased expression of estrogen-response-element gene C3 or androgen-response-element gene Rhox5, respectively, in both WT and KO mice fed control or Montgomery diets, indicating that bone protection is not due to estrogenic/androgenic actions of the diet.
Conclusion and Potential Impact:
Montgomery diet prevented bone loss due to sex steroid deficiency fully in females and partially in males. Thus, optimal skeletal benefits might be achieved by tailoring antioxidant-rich diets to patients of either sex.
Impact of Hepatic Stellate Cells in Scaffold-Free 3D-Bioprinting of the Liver Model
Authors: Koehler Cutter J. , Zhang Wenjun , Walsh Julia R. , Naqvi Raza A. , Gramelspacher Erika , Smith Lester J. , Li Ping , Ekser Burcin 
Published: January 2019

Background and Hypothesis: Hepatic stellate cells (HSC), which compromise ~15% of liver cells, are vital to hepatocellular function. Scaffold-free 3D-bioprinting (SF3DBP) offers an avenue for the creation of realistic organ models without the use of biomaterials. Therefore, we hypothesized that co-culturing primary hepatocytes with HSC in SF3DBP liver model would uphold hepatocyte function over time, providing us a better 3D-liver model for research.
Experimental Design: We used freshly thawed primary pig hepatocytes and immortalized pig HSC to generate spheroids with hepatocytes alone, HSC alone, or a combination of hepatocytes and HSC (2.5:1 ratio). Spheroids were formed using low adhesion plates, then characterized for distance from well center, diameter, roundness, and smoothness. A column of spheroids was printed using a Regenova 3D-bioprinter. Remaining loose spheroids are incubated over two weeks for albumin secretion, mRNA transcription, and histological analysis.
Results: Co-cultures of hepatocytes and HSC (2.5:1 ratio) formed spheroids within 48 hours, as did HSC only spheroids (Figure 1). Spheroids composed of only hepatocytes failed to form round spheroids. The combination spheroids increased in roundness and decreased in diameter between characterizations over 6 days.
Conclusion and Potential Impact: Spheroids proved too large to print at 48 hours but were successfully recognized and placed by the 3D-bioprinter. SF3DBP of combination spheroids would be viable by day 6. Optimization of spheroid composition using different cell ratios including HSC, hepatocytes, liver sinusoidal endothelial cells and fibroblasts, as well as optimization of spheroid incubation time will allow for production and printing of more advanced liver models.
Genetic Defects in SHROOM3 Lead to Congenital Heart Defects
Authors: Lorentz Samuel , Durbin, MD, MS Matthew D. , Ware, MD, PhD Stephanie 
Published: January 2019

Background and Hypothesis: Congenital heart disease(CHD) is the most common birth defect, but most genetic contributors remain unknown. We recently identified CHD patients with variants in a gene called SHROOM3. The SHROOM3 protein impacts the actin cytoskeleton by binding ActinF and Rho-kinase, causing actomyosin constriction. SHROOM3 also binds Dishevelled2(Dvl2), a component of Wnt/Planar cell polarity(PCP) signaling pathway, suggesting a connection between PCP signaling and actin-myosin contraction. We hypothesize SHROOM3 disruption alters PCP signaling and actin cytoskeleton during cardiac development, and is a novel contributor to CHD.
Project Methods: We analyzed the cardiac phenotype of Shroom3 gene trap knockout mice at embryonic day 14.5. We characterized the expression of Shroom3 during cardiac development using LacZ staining at important stages of cardiac development. Using IHC, we measured actomyosin disruption in Shroom3 knockout embryos. We preformed in silico analysis on previously identified SHROOM3 variants from patients with CHD.
Results: Shroom3 null mice had Ventricular Septal Defects (0.73, p=0.0006), Double Outlet Right Ventricle (0.33, p=0.04), Left Ventricular Noncompaction, and other CHD. Shroom3 mutant mice left ventricular wall thickness was 36% thinner compared to wild type mice (99.0±8.6µm, 63.0±8.4µm, p=0.005). LacZ shows the expression of Shroom3 through important stages of cardiac development, and IHC shows actomyosin disruption. In silico analysis demonstrates CHD patients have SHROOM3 variants in highly conserved nucleic acid and protein sequences, and significant protein structural changes.
Conclusion and Potential Impact: Shroom3 null mice have cardiac defects resembling a Wnt/PCP disruption phenotype. Similarly, patients with CHD have likely pathogenic variants in SHROOM3. These data support a role for SHROOM3 in CHD pathogenesis and begin to elucidate mechanisms. Identifying SHROOM3’s role in CHD is critical to understanding cardiac development as well as the diagnosis, management and treatment of CHD.
Effect of Signal-Dependent Noise on Phase Synchrony Pattern
Authors: Misiolek Kalina A. , Rubchinsky Leonid L. , Worth Robert M. 
Published: January 2019

Background: Intermittent phase synchrony is a phenomenon that occurs at subthreshold levels of oscillator coupling, where two oscillators appear to be synchronized at some times and desynchronized at others. Here, periods of “synchrony” are defined by a certain amount of statistically significant correlation between the time series of the oscillators.1 While general synchrony is observable in any number of settings (e.g. coupled pendula), intermittent synchrony has been detected in EEG readings from specific pairs of electrodes from patients with schizophrenia and Parkinson’s Disease.1 However, the extent to which EEG noise impacts synchrony pattern within the Rubchinsky et. al. model has not yet been studied.1
Methods: Using non-experimental data in MATLAB, we propose to run a series of trials to study the effect of signal-dependent multiplicative noise on the patterns of phase synchrony between oscillators. In the first condition, we simulate two completely synchronized signals, add signal-dependent noise to one, and observe the resulting changes to the synchronization pattern. In the second condition, we begin with two completely desynchronized signals.
Potential Impact: In studies of intermittent phase synchrony, it has been suggested that this pattern is the result of neuronal circuits which, as the EEG signals synchronize, fire more strongly and as a result become less responsive to outside input. This interpretation has the power to explain some of the symptoms experienced by patients. Thus, the specific pattern of synchronized and de-synchronized episodes is potentially highly significant. Our study is a necessary first step to understanding if the existing model and interpretations are accurate.
References:

Rubchinsky, L. L., Ahn, S., & Park, C. (2014). Dynamics of desynchronized episodes in intermittent synchronization. Frontiers in Physics, 2. doi:10.3389/fphy.2014.00038
Minimally Invasive, Non-Terminal In Vivo Muscle Testing of a Porcine Tibia Fracture Model
Authors: Peters Alexander W. , Corona Benjamin T. , Milto Anthony J. , Tucker Aamir , Brinker Alex , Savaglio Michael , Adam Gremah , Ganesh Venkateswaran , Gunderson Zachary , Childress Paul , Natoli Roman M. , McKinley Todd O. , Kacena Melissa A. 
Published: January 2019

Background and Hypothesis: Soft tissue injury surrounding tibia fractures is a key determinant of surgical care decisions and healing outcomes. We have established a porcine tibia fracture model with a corresponding volumetric muscle loss (VML) injury in the adjacent peroneus tertius (PT) muscle. Herein, we test the hypothesis that tibia fracture without VML induces an initial strength deficit that recovers within three months post-injury, while VML injuries present chronic strength deficits.
Experimental Design or Project Methods: 15 castrated Yucatan minipigs pigs will be evaluated in the following groups: Tibia defect (TD)-only, TD+small VML, and TD+large VML. To date, 12 have undergone injury, and 3 have completed the study (TD-only, n=2; TD+small VML, n=1).
In vivo muscle testing of the anterior compartment of the lower hindlimb was performed before and 1, 2, and 3 months post-injury.
Results: Before injury the non-operative and operative limbs had similar peak muscle strength (11.8±1.0 vs. 10.8±0.6 Nm; p=0.42), and non-operative limb strength did not change during the study (ANOVA p=.89). Relative to pre-injury values, the tibia defect with VML injury presented 71, 77, and 79% strength loss, while the tibia defect-only limbs presented 46, 60, and 48% strength loss at 1, 2, and 3 months post-injury, respectively.
Conclusion and Potential Impact: The data are limited by low sample sizes as this project is ongoing. Preliminary data do not appear to support the hypothesis, as limbs with TD-only presented persistent strength deficits, though potentially of lesser magnitude than VML injured limbs. The mechanism of strength loss following TD-only may be related to disuse.