bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence Of Product Innovation And Price On Customer Satisfaction In Halodoc Health Application Services During Covid-19 (Survey Of Halodoc App Users In Bandung In 2021)
Authors: Et. al. Didi Tarmidi
Published: January 2024

This research was conducted to find out how much influence product innovation (X1) and Price (X2) on Customer Satisfaction (Y) on Halodoc application in Bandung. The method used in this study is a quantitative method with 100 respondents of Halodoc application users in Bandung with multiple regression analysis calculations processed in SPSS25 Windows software. The main data from the study used questionnaire surveys, and secondary data was obtained through journal publications, articles, and theory books. According to the results of this study shows that the variable Product Innovation (X1) and Price (X2) has a significant influence together on the variable Customer Satisfaction (Y). These results showed the researchers that halodoc application users in Bandung considered the perspective when assessing satisfaction in using a product such as Product Innovation and Price offered.
Uplink Performance Of Coordinated Multipoint In 5G Cellular Network
Authors: Alshantti Mohammed
Published: January 2024

The study aims to study the uplink performance of coordinated multipoint in 5G cellular network. Nonetheless, this approach cannot deal with inter-cluster intrusion, and adjusts only the cell borders of the interference. In the other side, because CoMP relies on static clusters and the whole spectrum is dedicated to each, we cannot ignore the issue of edge MS, whether for full spectrum, quasi-static, or non-spectrum systems. Clustering of spectrum distribution is mentioned here; issues with the CoMP approach are discussed in this paper. One-to-many point-to-many grid network grid network (B4G/5G) is essential in connecting disparate geographical locations. The prior studies have analyzed how to better load-balancing would help with static fault tolerance and improve device throughput were concerned.  We expand the cooperating collection when needed to service traffic on demand, dynamically composing the cells on the base stations in order to give cells more transmit power for larger scale operations or to accommodate more users. Doing it dynamically in real-time to manage members' radio energy more effectively enables the device to offload traffic through usable cells to eliminate capacity concerns.  There are two kinds of methods of clustering MSs according to their movement speeds: In the low mobility method, hybrid cells are found for each subband; in the high mobility approach, a new configuration of subbands is chosen to overcome an unanticipated shift in mobility The Monte Carlo simulations have proof and demonstrate our next-generation connectivity ability. The current approaches demonstrate an improvement in device throughput, radio resource consumption, and electricity usage, which means they are beneficial when it comes to overall energy efficiency. As a result, an alternative that is both intra- and inter-cluster conflict is presented to the Cloud Radio Access Network (C-RAN) is introduced to counter both demand and power fluctuation—dynamic joint processing.
Resistant arterial hypertension: modern view of the problem
Authors: Kuchmin Alexey N. , Diskalenko Olga V. , Izotova Anna B. , Morozov Sergey L. , Ekimov Vitaly V.
Published: January 2024

In clinical practice, uncontrolled arterial hypertension remains a difficult but solvable task, given the available arsenal of antihypertensive drugs. However, resistant arterial hypertension is diagnosed in 10%–15% of these cases. A significantly higher risk of cardiovascular complications indicates the extreme importance of the successful treatment of this pathology. Resistant hypertension is defined as above-goal high blood pressure in a patient despite concurrent use of three antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a renin–angiotensin blocker (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. All antihypertensive drugs should be administered at maximum or maximally tolerated doses. Resistant hypertension also includes cases in which blood pressure targets are achieved with ≥4 antihypertensive medications. The diagnosis of resistant hypertension requires assurance of antihypertensive medication adherence and exclusion of the “white-coat effect” (office blood pressure above goal but out-of-office blood pressure at or below the target). Once antihypertensive medication adherence is confirmed and out-of-office blood pressure recordings exclude a white-coat effect, the evaluation includes the identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. The management of resistant hypertension includes the maximization of lifestyle interventions, correction of sleep disorders, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower blood pressure if blood pressure remains high.
Method of forecasting the durability of road structures
Authors: Ermoshin Nikolay A. , Kirillova Diana Yu.
Published: January 2024

Aim: This article is proposed method for studying the durability of road structures in order to ensure reliability and accident-free operation of highways.
Materials and Methods: The problem of durability assessment is solved by methods of the theory of Markov random processes.
Results: The result of the work is a mathematical formulation of the problem of predicting the residual resource (durability) and a method for solving it.
Conclusion: The method makes it possible to justify options for road and bridge structures that have the required durability while minimizing resource consumption.
Linear generator for power supply to on-board consumers of high-speed magnetically levitated carriages
Authors: Nikitin Victor V. , Zhao Tianzhong
Published: January 2024

Background: Maglev transport is a promising mode of transport that can provide passenger and freight transportation at speeds of up to 400-500 km/h, and in the longer term – up to 1000 km/h. Active research in this area is being conducted in China, Japan, and the USA. Currently, in China and Japan, speeds of 450-500 km/h have been achieved for commercial transportation, and promising programs have been adopted for the construction of high-speed maglev tracks and the creation of rolling stock. At such speeds, one of the pressing problems is the problem of contactless energy transfer for on-board consumers located on the carriage, because it is very difficult to ensure reliable contact current collection at speeds of 450-500 km/h and above. Aim: development of the design, calculation and analysis of the characteristics of a linear generator of electrical energy for contactless power transfer to the moving crew of high-speed magnetically levitated transport. Materials and methods: to calculate the external magnetic field of the linear generator inductor and the EMF induced in the receiving coil of the crew, methods of electromagnetic field theory and electrical circuit theory were used; calculation algorithms are implemented in the Visual Basic for Applications software environment. Results: a design was proposed and the calculation of the external magnetic field of an inductor with transposition of conductors was performed; to increase the EMF induced in the receiving coil of the crew, it is proposed to give the receiving coil a double 8-shape; the most rational inter-circuit distance of the linear generator inductor has been established; the nature of the change in the magnetic flux penetrating the receiving coil when the vehicle moves, and the magnitude of the emf induced in the receiving coil are determined. Conclusion: the results can be used in the development of rolling stock for promising high-speed maglev transport systems.
Numerical analysis of the influence of radiation defects on the transport characteristics of a superconducting CORC-cable
Authors: Mikhailova Irina K. , Martirosian Irina V. , Rudnev Igor A. , Pokrovskii Sergey V.
Published: January 2024

Aim: development of a simultaneous model, calculation and analysis of heat losses of a superconducting CORC cable based on standard HTSC tapes and irradiated HTSC tapes in cyclic load modes for magnetic energy storage system.
Methods: the CORC cable based on industrial original HTSC tapes and HTS tape with defects from irradiation is considered; to describe the electromagnetic and thermal characteristics of the system are used following methods: the concepts of the macroelectrodynamics, the fundamentals of the applied superconductivity, the finite element method are used; the calculation is implemented in the COMSOL Multiphysics.
Results: a model was developed, the optimal cooling mode was determined in 5 load cycles, it was shown that the presence of artificial pinning centers can significantly improve the thermal stabilization of the system and leads to a reduction in heat losses with the considered cooling schemes.
Conclusion: the results can be used in the development of the magnetic energy storage system based on high-temperature superconducting composites (HTS).
Implementing Non-Poissonian Forecasts of Distributed Seismicity into the 2022 Aotearoa New Zealand National Seismic Hazard Model
Authors: Iturrieta Pablo , Gerstenberger Matthew C. , Rollins Chris , Van Dissen Russ , Wang Ting , Schorlemmer Danijel
Published: January 2024

Seismicity usually exhibits a non-Poisson spatiotemporal distribution and could undergo nonstationary processes. However, the Poisson assumption is still deeply rooted in current probabilistic seismic hazard analysis models, especially when input catalogs must be declustered to obtain a Poisson background rate. In addition, nonstationary behavior and scarce earthquake records in regions of low seismicity can bias hazard estimates that use stationary or spatially precise forecasts. In this work, we implement hazard formulations using forecasts that trade-off spatial precision to account for overdispersion and nonstationarity of seismicity in the form of uniform rate zones (URZs), which describe rate variability using non-Poisson probabilistic distributions of earthquake numbers. The impact of these forecasts in the hazard space is investigated by implementing a negative-binomial formulation in the OpenQuake hazard software suite, which is adopted by the 2022 Aotearoa New Zealand National Seismic Hazard Model. For a 10% exceedance probability of peak ground acceleration (PGA) in 50 yr, forecasts that only reduce the spatial precision, that is, stationary Poisson URZ models, cause up to a twofold increase in hazard for low-seismicity regions compared to spatially precise forecasts. Furthermore, the inclusion of non-Poisson temporal processes in URZ models increases the expected PGA by up to three times in low-seismicity regions, whereas the effect on high-seismicity is minimal (∼5%). The hazard estimates presented here highlight the relevance, as well as the feasibility, of incorporating analytical formulations of seismicity that go beyond the inadequate stationary Poisson description of seismicity.
Plaque Patterned Cutaneous Candidiasis on the Lower Legs: A Case Report
Authors: Sung Jae Young , Lim Ji Won , Kim Chang Yong , Cho Young Ah , Lee Yang Won , Choe Yong Beom , Yu Da-Ae
Published: January 2024

Diabetes mellitus (DM) is a metabolic disorder that causes chronic hyperglycemia, leading to immune dysfunction and increased vulnerability to infections. As a result, patients with DM are more susceptible to fungal infections, including Candida species, due of their weakened immune systems. Cutaneous candidiasis is a fungal infection that appears as a red plaque with peripheral satellite papules and pustules around the periphery. Patients with chronic mucocutaneous candidiasis may have erythematous plaques and thickened skin thickening with an overlying scale, which can mimic plaque psoriasis. Therefore, fungal infections should be considered when assessing chronic refractory psoriasiform lesions that are difficult to treat, especially in patients with DM. This report describes a case of cutaneous candidiasis in both lower legs, which was initially misdiagnosed as psoriasis.
MODEL PEMBELAJARAN ORICON SEBAGAI PERSPEKTIF BARU DALAM MENUMBUHKAN KEMAMPUAN BERPIKIR SEJARAH SISWA
Authors: Utari Shela Dwi , Widiadi Aditya Nugroho , Hudiyanto Reza
Published: January 2024

Abstract:Today's development of history learning is very complex, primarily when the independent curriculum is implemented. Students must possess various skills based on learning outcomes in the independent curriculum. One of those skills is historical thinking skills. Based on observations, it was found that teachers still need to learn about historical sources, even though this is very important in learning history. This void raises the problem that students need help to think historically. Based on this, the author wants to develop a learning model with a new perspective by applying historical sources in the learning process. The method used in this study is qualitative, with data collection techniques in the form of distributing questionnaires to history teachers. The data obtained is analyzed through three stages: the data reduction stage, data presentation, and conclusions. The result of this article is that there is a recommendation for the new learning model, Oricon. This Oricon model has five aspects: orientation, identification, collecting, construction, and evaluation. This model can be used by using historical learning resources following the material the teacher wants to explain to foster historical thinking skills. Then students will interact directly and reconstruct historical narratives from sources that have been found. Abstrak:Perkembangan pembelajaran sejarah saat ini sangat kompleks utamanya ketika kurikulum merdeka diberlakukan. Terdapat berbagai keterampilan yang wajib dimiliki oleh siswa berdasarkan capaian pembelajaran pada kurikulum merdeka. Salah satu dari keterampilan itu adalah keterampilan berpikir sejarah (historical thinking skills). Berdasarkan hasil observasi ditemukan guru masih jarang sekali menggunakan sumber sejarah padahal hal ini sangat penting dalam pembelajaran sejarah. Adanya kekosongan ini menimbulkan sebuah permasalahan bahwa siswa belum memiliki kemampuan berpikir sejarah. Berdasarkan hal tersebut penulis ingin mengembangkan sebuah model pembelajaran dengan perspektif baru dengan menerapkan sumber sejarah dalam proses pembelajaran. Metode yang digunakan dalam penelitian ini adalah kualitatif dengan teknik pengumpulan data berupa menyebarkan angket kepada guru sejarah. Data yang diperoleh dianalisis melalui tiga tahap, yaitu tahap reduksi data, penyajian data, dan penarikan kesimpulan. Hasil dari artikel ini yaitu adanya sebuah rekomendasi model pembelajaran baru yaitu Oricon. Pada model Oricon ini terdapat lima aspek yaitu orientasi (orientation), identifikasi masalah (identification), merencanakan dan mengumpulkan informasi (collecting), mensitesis informasi (construction), serta evaluasi (evaluation). Model ini dapat digunakan dengan menggunakan sumber belajar sejarah sesuai dengan materi yang ingin dijelaskan oleh guru sebagai upaya menumbuhkan kemampuan berpikir sejarah. Kemudian siswa akan berinteraksi secara langsung dan merekonstruksi narasi sejarah dari sumber yang telah ditemukan.
ANALISIS PEMANFAATAN CHATGPT DALAM PEMBELAJARAN SEJARAH OLEH MAHASISWA PROGAM STUDI PENDIDIKAN SEJARAH UNIVERSITAS JAMBI
Authors: Meihan Andre Mustofa , Sinurat Junita Yosephine , Rukmana Lisa
Published: January 2024

Abstract: Various technological advances in the education make it easier for students to get various reference sources to help with the learning process. This research aims to analyze the use of ChatGPT by students of the History Education Study Program at Jambi University. As well as looking at the potential risks in using ChatGPT in history learning. In this research, quantitative approach was used. The data were collected by surveys and literature studies. We distributed questionnaires to students. analyzed the results referring to the findings from literature review that have been carried out by researchers. Based on the findings and discussions, it can be concluded that: all students know about the existence of the ChatGPT. The majority of them (45.5 percent) use ChatGPT to obtain information related to learning. The intensity of students using this application is included in the frequent category (50.9 percent). By using ChatGPT students feel helped in learning and obtaining information with a percentage reaching 81.8 percent. Apart from its many benefits, in fact the use of ChatGPT in education also poses various kinds of potential risks. So there needs to be supervision for students when using this application, so that academic ethical and moral values are maintained and upheld so that what they do brings benefits. Abstrak: Berbagai kemajuan teknologi di bidang pendidikan memudahkan mahasiswa untuk mendapatkan berbagai sumber referensi untuk membantu proses pembelajaran. Penelitian ini bertujuan untuk menganalisis pemanfaatan ChatGPT oleh mahasiswa Program Studi Pendidikan Sejarah Universitas Jambi. Serta melihat potensi risiko dalam menggunakan ChatGPT dalam pembelajaran sejarah.  Pada penelitian ini akan digunakan pendekatan kuantitatif. Data dikumpulkan melalui survei dan studi literatur. Kami membagikan kuesioner kepada mahasiswa. Hasil analisis mengacu pada temuan dari tinjauan pustaka yang telah dilakukan peneliti.Berdasarkan temuan dan pembahasan dapat disimpulkan bahwa seluruh mahasiswa mengetahui keberadaan ChatGPT.Mayoritas dari mereka (45,5 persen) menggunakan ChatGPT untuk memperoleh informasi terkait pembelajaran. Intensitas mahasiswa menggunakan aplikasi ini termasuk dalam kategori sering (50,9 persen).Dengan menggunakan ChatGPT mahasiswa merasa terbantu dalam belajar dan memperoleh informasi dengan persentase mencapai 81,8 persen. Selain banyak manfaatnya, nyatanya penggunaan ChatGPT dalam dunia pendidikan juga mempunyai berbagai macam potensi resiko. Maka perlu adanya pengawasan bagi mahasiswa dalam menggunakan aplikasi ini, agar nilai etika dan moral akademik tetap terjaga dan dijunjung tinggi agar apa yang dilakukannya membawa manfaat.
The determinants of regional migration in Croatia
Authors:   University of Primorska, Faculty of management, Koper, Slovenia, Grdović Gnip Ana
Published: January 2024

Migration has had a great impact on Croatia, especially after it joined the EU. Thus, several studies have focused on international migration compared to regional migration which is under investigation. This study sheds some light on the determinants of internal migration at the NUTS3 level in Croatia in the 2000-2019 period relying on a fixed effects panel estimation. The results show that regional migration in Croatia is in line with the stylized facts on migration. The living standard and (labour) productivity measures, along with employment and wages are the main economic drivers of migration inflows and outflows. However, regions with substantial tourism activity attract inflows and disincentivize outflows of people, while regions with a high share of agriculture, forestry, and fisheries in the value-added decrease internal migration inflows. Moreover, environmental protection results also being a significant determinant of regional migration.
Retrospective Analysis of COVID-19 Impact on Social + Emotional Development in Children of Low-Income Communities from Head Start
Authors: Li Gabrielle S. , Sanapati Satya P. , Han Amy
Published: January 2024

Background:Geminus Head Start is a federal program that works with children under five years old from low-income communities to promote school readiness. The organization in Northwest Indiana provided anecdotal data on delayed social and emotional development of children during the pandemic. Studies have shown that adverse childhood development can have a severe psychological and physiological impact on health outcomes into adulthood. However, there has been a lack of research on quantifying the extent of damage from the pandemic on our Head Start children, who mainly identify as Black/African American.
Methods:Geminus Head Start provided demographic data including race, postal codes and DECA for over 4650 students from 2019-2023. DECA, Devereux Early Childhood Assessment, is used by educators to evaluate children’s social emotional competence for early intervention. In this study, we are investigating the DECA categories, including initiative, self-control, and attachment/relationships. We analyzed DECA scores via ANOVA along with listening into the teacher focus groups.
Results:Students had increased attachment/relationship scores from the 2019-2020 school year to the 2020-2021 school year (36.69 to 44.59). However, following COVID-19 to the 2021-2022 and 2022-2023 school years, these scores dropped to 23.51. When looking at the second protective factor, self-regulation, the opposite trend was found. The scores went from 18.79 in 2019-2020 down to 14.68 in 2020-2021 and eventually up to 23.51 in 2021-2022.
Conclusion:Like most institutions, the pandemic has created a time of isolation and instability for our children and their families. In particular, these children have not been able to access adequate conditions to develop emotional and social maturity. Lacking this development can lead to several negative health outcomes as it may impact mental health and the ability to create healthy supportive networks.
Clinical Features for Detecting Diabetic Macular Edema using Artificial Intelligence
Authors: Liu Jeffrey , Salem Doaa Hassan , Jill Hunter , Janga Sarath Chandra , Hajrasouliha Amir
Published: January 2024

Background:Vision is a valuable part of life: influencing our perception of the world and of memories. Diabetes, and more specifically, Diabetic Retinopathy (DR) can affect our vision, taking away sight potentially permanently if left untreated. Currently, Diabetic Retinopathy is the leading cause for adult blindness and will continue to rise with increasing prevalence of adult diabetes. Diabetic Macular Edema (DME), a complication of DR, is diagnosed by ophthalmologists using optical coherence tomography (OCT); however, the sheer amount of DME-related imaging creates a time strain on ophthalmologists, creating a demand to further optimize the image reading process. In this study, we hypothesize that increasing the rate and ease of diagnosing DME by introducing artificial intelligence-based methods in primary medical clinics will increase the long-term preservation of ocular health in diabetic patients.
Methods:Due to the nature of our retrospective cohort study, consent was not acquired and images were also de-identified. We categorized 676 patient files by HbA1c, non-proliferative diabetic retinopathy (NPDR) severity, and proliferative diabetic retinopathy (PDR). Retinal OCT images were annotated to identify central macular edema, a common feature of DME. Retinal fundus images were also annotated to identify microaneurysms and hemorrhages, two additional features commonly used for detecting either DR or DME.
Results:A lesion features dataset was prepared to train our AI model. OCT and fundus imaging features were extracted and combined to train the AI model for DME detection. From annotations of the in-house Macular thickness dataset, it was seen that 167 patients had DME from the total 389 diabetic retinopathy patients.
Conclusion:We will continue to prepare more datasets like the macular thickness dataset for our AI. We predict that after our AI receives substantial training with the datasets, the AI will potentially demonstrate some capability of diagnosing DME, supporting its use in medical diagnostics.
Investigating the Functional Impacts of Metabolic Disease Associated Immune-Vascular Interactions in Alzheimer’s Disease
Authors: Maag Garrett , Paraiso Hallel C. , Huang Hannah , Yu I-Chen Ivorine
Published: January 2024

Background and Hypothesis:Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with undefined etiology and is the fifth leading cause of death worldwide. AD pathology is characterized by amyloid-beta (Aβ) plaques. Previous work demonstrated that alterations in the microvasculature are some of the earliest recognizable changes in AD, and that most patients with dementia have mixed vascular pathologies. We investigated the functional impacts of metabolic disease associated immune-vascular perturbation on the underlying mechanisms of AD.
Methods:Adult male Leprdb/J (db/db) were obtained from the Jackson Laboratory. Activated microglia and brain vessel density levels were assessed using immunofluorescence. Cerebral microvessels were isolated for RNA examination using qPCR, and FACS-based analysis of brain endothelial cells. Immunofluorescence of hAβ42 transport in microvessels were observed via confocal microscope. Quantification of images were performed using Fiji (NIH) software.
Results:Db/db mice brains displayed higher levels of activated microglia with increased soma area and decreased circularity (p<0.05). This confirms early vascular stress leads to increased immune cell activation. Brain vessel density analysis revealed a non-statistically significant trend with decreased density in db/db mice. Given that functional changes occur before structural changes, we shifted our examination to the microvasculature. Brain microvessels were isolated and validated and both qPCR and FACS results demonstrated increased levels of inflammatory mediators and cell adhesion molecules in db/db mice (p<0.05), confirming microvessel dysfunction and neuroinflammation. Finally, quantification of luminal area fluorescence demonstrated decreased hAβ42 transport in db/db mice (p<0.01), validating functional disturbance in the cerebral microvasculature.
Conclusion and Impact:The vascular risk factors of metabolic disease can lead to dysfunction and inflammation in cerebral microvasculature, causing accelerated progression of AD. Our results emphasize the contributory role of cerebral small vessel health in the origin and evolution of AD and present an opportunity for novel development of surrogate biomarkers and therapeutic treatments.
Radiological Findings in Patients Presenting with Brief Resolved Unexplained Events (BRUEs)
Authors: Mallin Stasia , Kambalyal Amogh , Holloran Tara , Newman Christopher , Marine Megan
Published: January 2024

Background/Hypothesis: Brief resolved unexplained events (BRUEs) are events in infants characterized by cyanosis, abnormal breathing, abnormal tone, and altered responsiveness. Practice guidelines define high-risk and low-risk BRUEs and do not recommend imaging in low-risk patients. We evaluated imaging in these patients and hypothesized that high-risk patients would have more imaging studies and abnormalities.
Methods: Using the radiology information system, a retrospective review was performed between 2016-2022 for patients <1 year presenting with BRUE. Defined search terms were used to identify imaging within one week of presentation. Patients were evaluated for clinical presentation, medical history, physical examination, imaging studies ordered, and final diagnoses.
Results: 126 patients were identified. 113 patients (46 female; 93 high-risk), between 3 and 355 days old (average age 97 days), met inclusion criteria. Imaging included chest radiographs (99), head CTs (24), brain MRIs (19), skeletal surveys (16), and others (22). There was no difference in the number of imaging studies obtained between these groups (p=0.423, Mann-Whitney U test). However, a greater proportion of high-risk patients had imaging abnormalities (p=0.023, Fisher’s exact test). Only 1/20 (5%) low-risk patients had abnormal imaging (PCR proven viral bronchiolitis). 26/93 (28%) high-risk patients had abnormal findings, most commonly on chestradiographs (15), brain MRIs (9), head CTs (4), and skeletal surveys (3). 18/26 high-risk patients had imaging abnormalities leading to a diagnosis other than BRUE (viral bronchiolitis, bronchopulmonary dysplasia, nonaccidental trauma, perinatal HSV infection, ventricular septal defect, double aortic arch, intestinal malrotation, and neurofibromatosis). Overall, 7/93 (7.5%) high-risk BRUE patients had significant pathology.
Conclusion: High-risk patients were more likely to have an imaging abnormality compared to low-risk patients, which is consistent with current imaging recommendations given only one low-risk imaging abnormality. Interestingly, 7.5% of the high-risk patients had significant pathology diagnosed by imaging.
Therapeutic Effects of a Placental Tissue-Derived Allograft on Fracture Healing
Authors: Morris Ashlyn , Ganguly Upasana , Margetts Tyler , Varner Will , Tucker Aamir , Harris Alexander , Nazzal Murad , Parker Reginald , Wang Hannah , Karnik Sonali , Blosser Rachel , Gergely Istvan , Nguyen Natalie , White Fletcher , Fehrenbacher Jill , Kacena Melissa
Published: January 2024

Background:As 5-10% of fractures will not heal without medical intervention, there is an ongoing need for effective treatments to promote fracture healing. CTM Biomedical produces human placental tissue-derived allografts that are used clinically and may assist in healing; however, no pre-clinical studies assessing these products have been performed. Our study investigating the impact of CTM products on the healing of a standard femoral fracture and a critical sized femoral defect (CSD) aims to fill this gap. We hypothesize that CTM product application will improve fracture healing and reduce pain-related behaviors.
Methods:Femoral fractures were induced in 45 mice. CTM membrane, CTM paste, a combination of CTM membrane and paste, or saline was applied to each fracture. X-rays were taken twice weekly over 22 days, and blinded modified Radiological Union Scale for Tibia (mRUST) fracture scoring was performed. Complete blood analysis was conducted weekly. Following euthanasia 23 days post-surgery, μCT and histomorphometric analyses were conducted. CSDs have also been surgically induced in the femurs of 95 mice, with plans for similar fracture analyses.
Results:CTM product application did not significantly alter the levels of inflammatory cells, suggesting that the mice did not undergo immunological reactions. mRUST scoring indicated that CTM products may not alter fracture healing rates. However, combined application of CTM membrane and paste significantly increased the fracture callus’s mineralized volume (by ~90%) and the percent of the callus that was bone. CTM membrane and paste application also led to an increased threshold for hind paw withdrawal, suggesting that CTM products may decrease pain-related behaviors.
Future Directions:We hypothesize that in our CSD model, mice treated with the combination of CTM membrane and paste will display improved fracture healing and decreased pain-related behaviors. If shown to be effective, CTM product use may decrease fracture nonunion risk and increase comfort.
Factors Contributing to Potentially Unnecessary Pediatric Emergency Transfers
Authors: Clements Kortni , Glober Nancy
Published: January 2024

Background: Riley Hospital for Children receives thousands of emergency pediatric transfers from outside hospitals every year. The United States is currently facing a national EMS shortage along with increasing costs of medical care. Additionally, these transfers can be inconvenient for patients and their families. However, not all of these transfers are medically necessary. Identifying factors that contribute to unnecessary emergency transfers is essential for optimizing care for each patient.
Methods: Retrospective chart reviews of electronic medical records at Riley Hospital for Children were completed for transferred patients between 01/01/2022 to 02/20/2022. Patients were identified through the transfer center patient list. The primary objective of the study was to identify patients transferred and discharged from the emergency department without advanced imaging or specialist consult. Demographic data including age, race, ethnicity, and sex were collected.
Results: There were 404 patients included in the study. About one third of these patients were discharged from the emergency department. Of those, 38 patients (9.4%) also did not have advanced imaging or a specialist consult in the Riley Emergency Department. Age was found tobe statistically different between these patients and all other patients. The median age for patients discharged without advanced imaging or specialist consult was 2.4 years old, while the median age for all other patients was 6.5 years old. Other demographics including race, ethnicity, and sex were not significantly different.
Conclusion and Potential Impact: The results suggest that younger pediatric patients may be at a greater risk for unnecessary emergency transfer. The generalizability of this study is limited in scope due to the use of only one EMR and hospital system. Finally, as this is a retrospective study, the information is limited by what was documented.
Preliminary Assessment of Cognitive Changes in Pediatric Cancer Survivors After a Neurocognitive Intervention
Authors: Clemmer Maddie , Romack Donna , Coven Scott , Koch Sarah , Sajdyk Tammy
Published: January 2024

Background: Pediatric patients with acute lymphoblastic leukemia (ALL) receive large doses of neurotoxic chemotherapy as part of their treatment. Though lifesaving, it can induce life-long issues. Cognitive deficits are one of the most common reported concerns in survivorship clinic among pediatric cancer survivors. One unique approach to improving deficits in cognitive functioning is The Mediated Learning Experience (MLE) developed by Reuven Feuerstein. MLE is based on neuronal plasticity. Findings from MLE studies have shown improvements in cognitive task performance, increases in daily functioning, and increased learning in patients with neurological impairment. However, MLE has never been administered to children or adolescent cancer survivors with cognitive deficits.
Methods: Survivors were recruited from the Survivor Clinic in IU North Hospital. Survivors were 10-16 years of age, English speaking, and reporting executive functioning issues in school. The intervention utilized was the MLE enrichment tool: Organization of Dots. Participants met with MLE certified mediators 30 – 40 minutes biweekly for 8 weeks. At 5 weeks, separate interviews were conducted with parents and participants to assess perceived changes in cognitive functions. These interviews asked participants to rate perceived changes on a Likert-type scale, which allowed for comparison of perceived changes reported by participants and parents.
Results: Four participants and their parents completed the 5-week interview. Preliminary results show participants and their parents perceive positive changes in the participants’ cognitive skills, new learning, motivation, transfer, metacognition, and active learning.
Conclusion/Potential Impact: Many pediatric cancer survivors experience cognitive deficits following their cancer treatment. There are limited options for these individuals for assistance in improving function, most of which are costly or difficult to access. The current study demonstrated that utilization of the MLE approach by Feuerstein can be a feasible option for filling the resource gap in neurocognitive rehabilitation.
Host-Implant Interaction Metabolite 10-HOME Mediated Dysregulation of Adiponectin Resulting in Breast Implant Associated Systemic Manifestations
Authors: Pulliam Ethan , Rinne Ethan , Khan Imran , Sinha Mithun
Published: January 2024

Background:Breast implant illness (BII) is a poorly understood systemic complication with unknown etiology. Surgical injury at the implant site initiates local inflammation, impacting adipose tissue through decreased adipose-derived adipokine expression. This acute stress responses activates lipid peroxidation pathways, generating oxylipins, causing inflammatory, nociceptive, and vascular responses to injury. One such oxylipin, (E)-10-hydroxy-8-octadecenoic acid (10-HOME), formed from oleic acid, is abundant in host-implant interaction. However, it is unclear how adipose inflammation is maintained. This study aims to elucidate how host-implant interactionmetabolites effect adiponectin expression, subsequently affecting T-cell differentiation eliciting an autoimmune state.
Methods:LiSa-2 (human derived adipose tissue secondary cell line) were grown in IMDM and RPMI (4:1) until confluent, then cultured in a well plate. Cultured cells were treated with 10μM 10-HOME for 48h, then were co-cultured with naïve T-cells (PBMC derived) for 48h. T-cells were harvested and flowcytometry was performed using CD4, CD184, CD194, CD196 markers and respective isotypes to verify differentiation (Th1, Th2, Th9/22). To study adiponectin gene expression, treated Lisa-2 cells were harvested for qRT-PCR. ELISA was performed using treated LiSa-2 culture media.
Results:We showed decreased expression of adiponectin, after 10-HOME treatment of LiSa-2 cells, compared to untreated cells. qRT-PCR (p=0.0022) showed downregulation of adiponectin gene transcripts in treated LiSa-2 cells, highlighting changes in modulation. Using ELISA (p=0.0006), the culture media of treated cells showed significantly less adiponectin than untreated media. Treated LiSa-2 cells led to polarization of naïve CD4+ T cells to Th1 subtype, evaluated by flowcytometry (p=0.0494). No significant difference in polarization was observed for Th2, Th9 and Th22 subtypes.
Conclusion:This study provides evidence that LiSa-2 with 10-HOME treatment caused increased Th1 polarization via modulation of adiponectin expression. Adiponectin regulates many inflammatory pathways, but its effect on Th-cell-mediated responses is poorly understood. Further studies should investigate the mechanism for adiponectin modulation causing T-cell imbalance.
Retrospective Analysis of COVID-19 Impact on Social + Emotional Development in Children of Low-Income Communities from Head Start
Authors: Li Gabrielle S. , Sanapati Satya P. , Han Amy
Published: January 2024

Background:Geminus Head Start is a federal program that works with children under five years old from low-income communities to promote school readiness. The organization in Northwest Indiana provided anecdotal data on delayed social and emotional development of children during the pandemic. Studies have shown that adverse childhood development can have a severe psychological and physiological impact on health outcomes into adulthood. However, there has been a lack of research on quantifying the extent of damage from the pandemic on our Head Start children, who mainly identify as Black/African American.
Methods:Geminus Head Start provided demographic data including race, postal codes and DECA for over 4650 students from 2019-2023. DECA, Devereux Early Childhood Assessment, is used by educators to evaluate children’s social emotional competence for early intervention. In this study, we are investigating the DECA categories, including initiative, self control, and attachment/relationships. We analyzed DECA scores via ANOVA along with listening into the teacher focus groups.
Results:Students had increased attachment/relationship scores from the 2019-2020 school year to the 2020-2021 school year (36.69 to 44.59). However, following COVID-19 to the 2021-2022 and 2022-2023 school years, these scores dropped to 23.51. When looking at the second protective factor, self regulation, the opposite trend was found. The scores went from 18.79 in 2019-2020 down to 14.68 in 2020-2021 and eventually up to 23.51 in 2021-2022.
Conclusion:Like most institutions, the pandemic has created a time of isolation and instability for our children and their families. In particular, these children have not been able to access adequate conditions to develop emotional and social maturity. Lacking this development can lead to several negative health outcomes as it may impact mental health and the ability to create healthy supportive networks.
Trends in Melanoma Patient Survival Based on Tumor Depth and Anatomic Location
Authors: Sarda Bhavi , Couetil Justin , Huang Kun , Zhang Jie , Alomari Ahmed K.
Published: January 2024

Skin cancer is the most common cancer. Melanoma composes less than 4% of total cases but is the cause of most skin cancer deaths. However, in the United States, melanoma has the fifth highest rate of incidence of all cancers with an average 93.5% 5-year survival rate. However, when melanoma spreads either to regional lymph nodes or to distant organs, the prognosis drops significantly, so there is a critical need to identify patients at risk for tumor spread. The objective of this research project is to determine the correlation between tumor depth and anatomic location with metastasis outcomes. We identified a cohort of 923 Stage 1 & 2 patients (those without lymph node metastases) from the Indiana University Simon Cancer Center Registry with an average follow up of 4 years (Std. dev = 3.2). We retrieved the clinicopathologic descriptions of their melanomas using a database from the IU Pathology department. Patients were stratified by tumor stage, location, and depth of invasion, and survival rates were analyzed Cox proportional hazard models and log-rank tests. Kaplan-Meier plots were generated with the survminer package. The results of the study indicate that there is no difference in metastasis for patients with similar levels of tumor invasion but different anatomic locations. Unexpectedly, multivariate cox regression showed that mitotic count was a stronger predictor of metastasis than tumor invasion. These results indicate that there is a need for bioinformatic tools to more accurately quantify semi-quantitative measures of tumor morphology. This would allow for rigorous research and higher precisions prognostic tools.
Blood Culture Contamination Rates in Bloomington, Association with Patient History
Authors: Schwieterman Vanessa , Lee Aimee , Motzkus Christine
Published: January 2024

Background/Objective: Blood cultures are vital for diagnosing infections and directing antibiotic therapy to causative organisms in systemically ill patients. Blood culture contamination contributes to increased costs, longer lengths of stay, and unnecessary antibiotic use. Certain patient histories and demographics have been associated with higher contamination rates. Identifying contamination risk factors within the hospital may allow for improvements in patient care.
Methods: Patient demographics, history, and blood culture information were identified through a chart review for all adult blood cultures collected in January 2023 at the IU Health Bloomington Hospital. Patient characteristics collected included age, race, ethnicity, BMI, and a number of comorbidities (COPD, diabetes, etc.). Blood culture characteristics, including the number of cultures drawn, hospital setting, etc., were also collected. A comparative analysis was performed between positive, negative, and contaminated cultures.
Results: In January, 443 adult patients had blood cultures collected at IUH Bloomington hospital, with contamination in 33 cases (7.4%). Patients with contaminated cultures had a higher prevalence of hypertension (75.8%) compared to those with negative cultures (61.9%). Type II diabetes was more prominent in the contaminated culture group (36.4%) than the negative culture group (31.3%). 15.2% of patients with contaminated cultures resided in extended care facilities, while only 12.3% of patients with negative cultures did so. Most contaminated cultures (97%) were drawn in the emergency department, with 3% collected in medical-surgical units/floor level of care.
Conclusion: Features of patient history, demographics, and culture collection may be associated with higher blood culture contamination rates.
Scientific/Clinical/Policy Impact and Implications: This data will be expanded into the entire 1st quarter of 2023 to further identify trends in culture contamination. Findings may present opportunities for quality improvement in patient care as IUH Bloomington looks to further reduce their rates of contaminated cultures.
Exploring a Transcriptome-forward Approach for Genetic Evaluation in Thoracic Aortopathy
Authors: Stanley Katherine , Landis Benjamin
Published: January 2024

Background/Objective: Thoracic aortic aneurysm (TAA) is an aortopathy that predisposes to aortic dissection and rupture. Transcriptomic analysis has diagnostic utility in other diseases, but this has not been developed for TAA. We therefore sought to implement the Genome Analysis Toolkit (GATK) as a tool for high-throughput detection of novel variants in RNA sequencing (RNA-seq) data from patients with TAA.
Methods: Human proximal aortic tissue samples from 63 TAA patients and 15 controls were used to establish primary smooth muscle cell (SMC) lines in culture. Total RNA was extracted at early passage; RNA-seq was performed using 150 base pair paired-end reads. Variants were called from RNA-seq reads using the GATK’s HaplotypeCaller tool. The MarkDuplicates tool tagged duplicate reads, but these were retained for variant analysis. Singletons were defined as heterozygous variants unique to one sample in the overall group.
Results: The RNA-seq pipeline was validated by confirming known mutations in 2 patients, inspecting reads directly in the Integrative Genomics Viewer (IGV), and genotyping for a common single nucleotide polymorphism. Across all 78 samples, the GATK pipeline identified 4,823,462 variant sites, 236,495 of which were in coding regions. Variant sites were filtered for those located within the coding regions of 31 genes curated for known evidence of aortic disease causality. Among the 511 coding variant sites in these genes, 330 single nucleotide variants and 33 insertions/deletions were identified as singletons. Singleton variant calls were evaluated for quality and annotated in order to predict their likelihood of pathogenicity, thus far identifying strong candidate causal variants in FBN1, TGFBR1, TGFB3, GATA4, and HEY2.
Conclusion: Application of the GATK RNA-seq pipeline expands our prior IGV analysis, further demonstrating the potential diagnostic utility of transcriptomic analysis of aortic SMCs in TAA.
Scientific Impact: Identifying novel aortopathy-associated variants could improve future disease detection and prediction of severity.