bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time to Diagnosis of Early-Onset vs. “Late-Onset” Colorectal Cancer: Is there a difference?
Authors: Chin Kayla L. , Myers Laura E. , Coffing Jessica M. , Larson Jason , Imperiale Thomas F. 
Published: January 2019

BACKGROUND
Colorectal cancer (CRC) incidence and mortality is increasing in persons ˂ 50 years old. Intervals between symptom onset and initial presentation (presentation interval [PI]) and between initial presentation and diagnosis (diagnosis interval [DI]) are not well-quantified.
OBJECTIVE
Compare PI and DI between early-onset CRC (EOCRC) and persons >50, and identify factors affecting these intervals.
METHODS
In this retrospective VA-based case-control study, we identified EOCRC cases from an ongoing study and compared them to controls (CRC patients aged ≥ 50 years). We abstracted demographics, clinical features, CRC location and stage, PI, and DI. Mann-Whitney tests compared mean and median PI and DI.
RESULTS
Advanced stage (III-IV) CRC was more common among the 240 EOCRC patients (mean age: 45.2, 60.8% White) than in the 234 controls (mean age: 63.8, 71.8% White): 55.4% vs 43.5%; P= 0.015. PIs and DIs, respectively, were present for 153(63.8%) and 222(92.5%) of cases and for 74(31.6%) 222(94.9%) of controls. No difference was found between median PI in EOCRC and late-onset CRC patients (42 vs 60 days, P= 0.68). The EOCRC cases had a significantly shorter median DI (41 [IQR = 16-83] vs 71 days [IQR = 32-145], P<0.0001).
CONCLUSIONS
In this retrospective study, younger patients had more advanced stage CRC at diagnosis than their older counterparts. However, contrary to published data, median time to diagnosis was shorter in those < 50 years. Factors associated with the DI are forthcoming. Candidate factors include race, diagnosis year, presenting symptoms, type of initial provider, CRC stage, and CRC location.
Examining Gross Anatomy Study Strategies Across Old and New Curricula
Authors: Davis, B.A. Elizabeth , Husmann, Ph.D. Polly R. 
Published: January 2019

Background and Hypothesis: In the fall of 2016, Indiana University School of Medicine implemented a new integrated curriculum. We hypothesized that the study strategies utilized by students for gross anatomy changed due to this redesign.
Project Methods: Students were given a voluntary survey about their study strategies, attitudes, and basic demographics near the end of their anatomy course. The students’ NBME and final course scores were also linked to their responses and responses were condensed into categories. Comparisons were made between students in the upper and lower thirds of the classes and between old and new curriculum cohorts.
Results: Several differences were found between the old and new curricula: use of web-based resources increased, self-quizzing decreased, and attendance decreased at a statistically significant level (p<0.0001, p=0.042, p<0.0001). Across both curricula, students who were more confident that they had studied enough going into the tests performed more poorly than those who were less confident (p<0.0001). Consistently the students in the top third of the class demonstrated total amounts of study strategies that were lower than in the bottom third of the class, though these results did not reach statistical significance (p=0.382).
Conclusion and Potential Impact: Student study strategies have changed between the previous and current anatomy courses in ways that may impact future student outcomes. More use of web-based resources may be of questionable quality and lead to more students feeling overwhelmed, while less self-quizzing may lead to less long-term retention of anatomy content. Metacognitive skills remain vital across curricula.
Genoproteomic analysis of leukemic cell response to Cytarabine reveals synergistic opportunities centered on cholesterol metabolism
Authors: Farmer Alex , Chen Fangli , Wu Xue , Rogozea Adriana , Ivan Mircea , Konig Heiko 
Published: January 2019

Background: Patients with acute myeloid leukemia (AML) carry a dismal prognosis due to drug resistant cancer cells that reside in O2 deprived niches of the bone marrow. Here, we sought to interrogate AML drug responses under hypoxic (1% O2) and normoxic (21% O2) conditions in order to identify novel drug targets.
Methods: We utilized RNAseq, PCR and RPPA to interrogate chemotherapy-induced expression responses in M14 cells. We further assessed intracellular cholesterol levels (ICCLs), cell growth and apoptotic cell death per MTT and FACS analysis in AML cell lines and primary cells (PCs) in response to chemotherapy under normoxia and hypoxia.
Results: Cytarabine blunted cholesterol biosynthesis- and induced CD36-mRNA expression under 1% and 21% O2. ICCLs were significantly higher in Cytarabine treated AML cells compared to untreated controls. Treatment with Rosuvastatin significantly inhibited growth of M14, THP1, OCI-AML3 as well as AML PCs (n=3). Further, Rosuvastatin lowered ICCLs and conferred pro-apopotic and growth inhibitory effects against M14 and THP-1 cells. Growth inhibition was enhanced when Rosuvastatin was combined with Cytarabine, yielding additive to synergistic effects. Similar effects were observed in AML PCs (n=10) where Rosuvastatin combined with Cytarabine demonstrated strong synergy.
Conclusion: (i) Depletion of ICCLs is counterbalanced by CD36 expression in Cytarabine-treated AML cells under normoxia and hypoxia. (ii) Rosuvastatin exerts antileukemic activity in AML cell lines and PCs via downregulation of ICCLs, induction of apoptosis and inhibition of cell growth. (iii) Rosuvastatin acts synergistically with Cytarabine against AML cells. Impact: Further investigation of Rosuvastatin in AML therapy is warranted.
Characterizing the Extent of Cell Death in Innate Immune Mediated Colitis
Authors: Hendrix Justin R. , Overstreet Anne-Marie , Boger-May Antonia , Boone David 
Published: January 2019

Background and Hypothesis:
Intestinal epithelial cell (IEC) turnover occurs every four-to-five days. In inflammatory bowel disease (IBD), IECs undergo increased cell death due to inflammation of intestinal villi and colonic crypts. This cell death leads to increased permeability of the intestinal barrier. This study examined the pathogenesis of IBD, focusing on innate immunity using mice with spontaneous innate immune colitis. The objective was to observe if there is a significant difference in expression of apoptosis in colitic mice vs. control mice.
Experimental Design:
Mice expressing the NF-kB inhibitor TNFAIP3 in the villi of IECs were interbred with RAG1-/- mice. TNFAIP3 x RAG1-/- (TRAG) mice developed 100% penetrant colitis by 6 weeks of age that was not observed in TNFAIP3 or RAG1-/- littermates. The presence of activated caspase-3 in distal colons was detected using immunofluorescence and quantified using ImageJ to compare differences between 4- and 8-week-old RAG vs.TRAG mice.
Results:
Increased numbers of caspase-3+ cells were found in TRAG mice compared to RAG mice. After treatment with antibiotics, similar levels of capase-3 were detected in both groups.
Conclusion and Potential Impact:
This investigation suggests that cell death in TRAG mice were increased due to deficient innate immunity in IECs. Thus, bacteria play a direct role by killing IECs or an indirect role by causing inflammation. Understanding how innate immune activation drives cell death in IECs, may lead to a better understanding of the complex regulation of IBD, and improved therapeutic agents targeting novel cell types in the remission of chronic IBD.
Leukocyte Localization in a Model of Innate Immune-Driven Colitis
Authors: Jones Jordan R. , Overstreet Anne-Marie C. , Boger-May Antonia M. , Boone David L. 
Published: January 2019

Background and Hypothesis:
Inflammatory bowel disease (IBD) is a disabling, chronic gut disorder involving immune dysregulation. Our lab has generated a murine IBD model in which the innate immune system drives inflammation. Innate lymphoid cells (ILCs), an innate immune cell subset that was recently discovered, exhibit many T-helper cell characteristics. ILCs, though few, produce cytokines, thereby significantly impacting tissue through local action in mucosal sites. They express the cell surface markers, CD90, which is unique to ILCs, and CD45, which all leukocyte types express. Colitis prevention in our model via ILC depletion indicates a role for ILCs in IBD. Therefore, we aimed to identify the ILCs’ localization in our murine model. We hypothesized that the ILCs will localize to inflamed areas of the intestinal lamina propria and into the intraepithelial spaces.
Experimental Design or Project Methods:
Mice expressing TNFAIP3, an inhibitor of NF-kB, were mated with adaptive immunity-lacking mice (RAG1-/-). RAG1-/- x Villin-TNFAIP3 (TRAG) mice had colitis that was 100% penetrant by age 6 weeks. Distal colons excised at age 4 weeks and 8 weeks were used for identifying CD45+ and CD90+ cells in both RAG and TRAG mice intestines via immunofluorescence.
Results:
We observed differences in the distributions of CD90+ and CD45+ cells within TRAG and RAG mice intestines.
Conclusion and Potential Impact:
Differences exist in intestinal leukocyte distributions within our models. Altered ILC distribution might reflect an inflammatory state or contribute to IBD pathology. This work may further elucidate ILCs’ role in IBD and as IBD treatment targets.
Birth Spacing and Family Planning: Implementation of enhanced education and training for Community Health Coaches
Authors: Jostes, BS BA Alexandra , Griffin, MS Wilma , Dechant, BS Paige , Otero, BA Carolina , Sobiech, PhD Kathleen , Chico, BA Denise V. , Litzelman, MD Debra 
Published: January 2019

Background: Indiana is ranked 43/50 for infant mortality in America. WeCare employs lay Community Health Coaches (CHCs) to promote positive behavioral changes in pregnant, postpartum and women of child-bearing age living in low-income, high-risk communities in order to reduce the risk of infant mortality. Infant mortality can be reduced in communities where birth spacing and family planning education are available.
Project Methods: The goal was to address the knowledge gaps in patient handouts and CHC training regarding birth spacing and family planning. Through extensive literature searches, case conferences with CHCs, and review of current training materials, five gaps in training were identified: (1) comprehensive knowledge of rapid repeat pregnancies (2) resources regarding contraceptive methods (3) contraceptive counseling in the antenatal and postpartum periods (4) joint decision-making models and (5) father involvement in family planning.
Results: With comprehensive literature reviews and collaboration with fellow WeCare members, the gaps in training were appropriately filled. The WeCare training manual for CHCs is updated with information regarding birth spacing and family planning, as well as with counseling techniques for contraceptive method decision-making. A gap in existing literature regarding father involvement in family planning was identified.
Conclusion and Potential Impact: By enhancing CHC education on birth spacing, family planning, and counseling techniques, we may begin to close the knowledge gap for women in low-income, high-risk populations. This has the potential to reduce the rate of rapid repeat pregnancies and unintended pregnancies. We have also opened a new avenue of research about father involvement in family planning in the US.
Store operated calcium entry in diabetic macrophages is reduced in fasting conditions
Authors: Lee Regina , Beli Eleni , Lee Chih-Chun , Kono Tatsuyoshi , Evans-Molina Carmella 
Published: January 2019

Background and Hypothesis:
In diabetic mice, intermittent fasting (IF) prevents diabetic complications by temporarily reducing inflammation during the fasting period. As calcium homeostasis is tightly connected to the inflammatory response, we hypothesize that IF regulates macrophage response by altering store-operated calcium entry (SOCE). SOCE, mediated by the STIM and ORAI families, is the primary form of calcium entry into the cell.
Experimental Design or Project Methods:
We assessed SOCE levels in control and diabetic (INS2Akita) mouse primary macrophages stimulated with a metabolic stimulus (MET: insulin, high glucose, palmitate) to mimic feeding and a starvation stimulus (STARVE: low glucose, low FBS, oleate) to mimic fasting. SOCE levels were measured by a Flexstation using Calcium-6 dye. We also assessed gene expression of SOCE components by RT-PCR and STIM1 and ORAI1 proteins by western blot.
Results:
A decrease in SOCE was observed with MET stimuli and an increase with STARVE stimuli in control macrophages. Interestingly, gene expression and protein levels of all major SOCE components, including STIM1 and ORAI1, were increased in the MET and decreased with STARVE. While diabetic macrophages had similar SOCE function than control under basal and MET conditions, they showed significantly downregulated SOCE under starvation conditions.
Conclusion and Potential Impact:
These data show that diabetic macrophages have altered SOCE function in response to fasting. This could have potential impact on how diabetic individuals respond to nutritional interventions such as IF that are recently proposed for prevention of diabetic complications.
Type 2 Diabetes Mouse Model: Insights into the Contribution of Metabolic Defects to Neurocognitive Decline
Authors: Loncharich Alexa , Reilly Austin , Yan Shijun , Ren Hongxia 
Published: January 2019

Background and Hypothesis: Metabolic diseases, including type 2 diabetes (T2D), have become increasingly prevalent and their associated medical costs have skyrocketed. Furthermore, recent epidemiological evidence suggests links between metabolic defects and neurodegenerative diseases, such as Alzheimer’s Disease (AD). The increasing coincidence of AD and T2D, and unmet treatment needs, necessitates research investigating potential shared mechanisms. To study glucose and lipid metabolism defects and neurocognitive deficits, we have generated non-obese insulin resistant mouse models, named GLUT4-mediated Insulin Receptor KnockOut (GIRKO). Insulin-responsive glucose transporter, Glut4, is expressed in muscle, fat, and a subset of neurons in the brain. Our previous publications show that GIRKO mice are highly insulin resistant and insulin sensitive GLUT4 neurons are critical mediators for glucose metabolism. We hypothesize that central insulin resistance in GIRKO mice instigates neurocognitive defects.
Experimental Design: We will measure the neurocognitive function of 3- to 4-month old GIRKO mice using Morris water maze (MWM) test.
Results: GIRKO mice exhibited increased escape latency. Additionally, they spent less time in the target quadrant in the probe trial, in which the platform is removed. GIRKO performed equally compared to control mice in raised platform tests, which demonstrates that motor competencies do not confound our findings.
Conclusion and Potential Impact: GIRKO mice have learning and memory deficits, which illustrates a possible link between neurocognition and metabolism. Our results support the notion that insulin resistance precedes cognitive decline and necessitates early intervention therapy to treat insulin resistance and protect cognitive function.
Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury
Authors: Luebbe Sam , Baker Hana E. , Mather Kieren J. , Goodwill Adam G. , Simon Blake R. , Earl Conner C. , Tune Johnathan D. 
Published: January 2019

Background and Hypothesis: Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study was designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury.
Experimental Design: Lean domestic swine received placebo (n=6) or canagliflozin (n=6; 300 mg PO) 24 hours prior to and the morning of an experiment. Hemodynamics, left ventricular pressure and volume were measured in open chest, swine at baseline, during a 60 min coronary occlusion, and during a 2-hour reperfusion period. The degree of myocardial infarction was assessed by staining with 1% tetrazolium.
Results: At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL; P < 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL; P < 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (P < 0.05) and stroke work (P < 0.05) relative to untreated controls swine during ischemia. SGLT2i decreased infarct size from 9.4 [Symbol] 2.1% in control swine to 3.1 [Symbol] 0.98% in SGLT2i treated swine.
Conclusion: SGLT2 inhibitors significantly improve cardiac contractile function and mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury in domestic swine.
Fidelity of Peer Supported Self-Management of Chronic Pain (Evaluation of a Peer Coach-Led Intervention to Improve Pain Symptoms—ECLIPSE)
Authors: Mannon, B.S. Joyce S. , Matthias, Ph.D. Marianne S. 
Published: January 2019

Background: ECLIPSE (Evaluation of a Peer Coach-Led Intervention to Improve Pain Symptoms) is a randomized controlled trial testing peer-supported chronic pain self-management. Veterans are paired with a peer coach (also with chronic pain) for 6 months. Peer coaches (PCs) and veterans meet or talk by phone 2x/month about pain self-management strategies, and veterans receive motivation and encouragement from their PC. To determine if the intervention was delivered as intended, fidelity was assessed at the end of the intervention period. Fidelity assessment is vital to help understand reasons for an intervention’s success or failure.
Methods: Intervention veterans were asked about the intervention’s delivery during their 6-month assessment, after intervention completion. Presence or absence of four “essential elements” of the intervention were evaluated, as well as meeting frequency.
Results: Scoring of veteran assessments revealed 74% of PC’s discussed self-management strategies and 69% of veterans felt motivated by their PC. Only 52% discussed how to adjust strategies and 34% discussed goal-setting. PC-veteran meeting frequency varied: 16% met weekly, 21% met twice a month, 16% met once a month, and 46% met less than once a month. 47% of PC’s had greater than 75% fidelity (i.e., the presence of at least 3 of 4 elements described above).
Conclusion and Potential Impact: About half of PC’s delivered the intervention with at least 75% fidelity. Fidelity was greater for discussing self-management strategies and motivating veterans. Results suggest that peer-supported self-management can be delivered with fidelity but PCs may need additional training to do so consistently.
MELodica Orchestra for DYspnea (MELODY): A Randomized Safety, Feasibility, and Efficacy Pilot
Authors: McGrath Mackenzie , Burns Debra S. , Crow Shannon , Lillie Aimee , Myers Laura J. , Myers Jennifer , Perkins Anthony J. , Rattray Nicholas , Smith Joseph , Wasmuth Sally , Bravata Dawn M. 
Published: January 2019

Background
Chronic obstructive pulmonary disease (COPD) is highly prevalent among Veterans. Patients with COPD commonly experience dyspnea, which can be debilitating and may limit daily activities leading to a reduced quality of life. Pulmonary rehabilitation often includes teaching pursed lip breathing as a method to reduce dyspnea. However, patients with COPD, including Veterans, have limited access to pulmonary rehabilitation due to transportation constraints and lack of referrals by physicians.
Methods
MELodica Orchestra for DYspnea (MELODY) is a randomized controlled clinical trial designed to assess the safety, feasibility, and efficacy of a music-based approach to teach pursed lip breathing to Veterans with COPD experiencing dyspnea. Patients will be randomized in a 1:1:1 ratio to the intervention group, education only control group, and usual care control group using block randomization. Patients in the intervention group will meet twice weekly over twelve weeks for instruction on how to play the melodica and to participate in group music-making. The program also includes education about COPD, pursed lip breathing, tobacco cessation, and other relevant topics. Each participant will receive quantitative assessments (e.g., exercise endurance and dyspnea scales) and participate in qualitative interviews.
Anticipated Results
We expect the intervention to be safe and feasible. We hypothesize that patients in the intervention group will achieve the greatest reduction in dyspnea compared with patients in either control group.
Potential Impact
If pilot data demonstrates efficacy, then a multiple-site randomized control trial will be conducted with intent to introduce the program into routine clinical practice.
Association of AHI and Other Patient Factors with Calvarial Thickness
Authors: Nag, BS Amit , Rabbani, MD Cyrus , Saltagi, MD Mohamad Z. , Schueth, BS Elizabeth , Nelson, MD, PhD Rick F. 
Published: January 2019

Background and Hypothesis: Temporal spontaneous cerebrospinal fluid (sCSF) leaks occur when spinal fluid leaks through defects in the skull base bone. Patients with sCSF leaks have approximately 22% thinner skulls but no change in extracranial bone thickness, suggesting an intracranial process causes skull thinning and the development of sCSF leaks. Approximately 83% of sCSF leak patients have obstructive sleep apnea (OSA) as measured by the apnea-hyponea index (AHI) and OSA is associated with spikes in intracranial pressure. We hypothesize that AHI is associated with isolated skull thinning in the general population.
Experimental Design: High resolution head CT images from patients with diagnostic sleep studies at IU health from 2010 to 2017 were analyzed (IRB approved) using 3D slicer to measure skull thickness of the squamous temporal bone. Age, body mass index (BMI), race and diabetes recorded. Mixed model analysis was used to determine the effect of a number of factors on skull thickness.
Results: 344 CT scans were analyzed. Increased AHI was significantly associated with thinning of the calvarium [2.68 mm - 0.003x, (x = AHI point) P<0.02], while thickening of the calvarium was associated with age [CI = 0.005 to 0.011 per year, P<0.001] and BMI [CI = 0.003 to 0.015 per mg/kg2, P<0.003]. Female gender (P=0.016) and diabetes (P=0.005) were linked to thickening of the calvarium. Hypertension had no effect on calvarial and zygoma thickness (P=0.244 and 0.575, respectively). The extracranial zygoma thickness was not associated with AHI (P=0.54) or BMI (P=0.811) but the zygoma thinned significantly with age [CI = -0.01 to - 0.002, P<0.002] and female gender (P<0.001).
Conclusion and Potential Impact: OSA is associated with skull thinning and may play a pathologic role in the development of sCSF leaks over time.