Proceedings of IMPRS最新文献

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Impact Of Connective Tissue Matrix Products and Critical Size Defects on Gut Microbiota and Fracture Healing in Mice 结缔组织基质产品和临界尺寸缺陷对小鼠肠道微生物群和骨折愈合的影响
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27940
Alexander Harris, Ashlyn Morris, Will Varner, Reginald S Parker, Murad K. Nazzal, Amy Creecy, Sonali J. Karnik, Rachel J. Blosser, Elizabeth Scott, Hannah S. Wang, Tyler J. Margetts, Marko Dragisic, Upasana Ganguly, Jill C. Fehrenbacher, Fletcher A. White, Jessica Hathaway-Schrader, Melissa A. Kacena
{"title":"Impact Of Connective Tissue Matrix Products and Critical Size Defects on Gut Microbiota and Fracture Healing in Mice","authors":"Alexander Harris, Ashlyn Morris, Will Varner, Reginald S Parker, Murad K. Nazzal, Amy Creecy, Sonali J. Karnik, Rachel J. Blosser, Elizabeth Scott, Hannah S. Wang, Tyler J. Margetts, Marko Dragisic, Upasana Ganguly, Jill C. Fehrenbacher, Fletcher A. White, Jessica Hathaway-Schrader, Melissa A. Kacena","doi":"10.18060/27940","DOIUrl":"https://doi.org/10.18060/27940","url":null,"abstract":"Abstract: \u0000Approximately 6.2 million people in the USA alone suffer from some form of fracture annually. Depending on the intensity of trauma and complexity of the fractures, some fractures will not heal without medical intervention. It is imperative to develop novel therapies that target fracture healing. Connective Tissue Matrix (CTM) Biomedical is a company that develops human placenta, amnion, chorion, and other umbilical derived allograft products which may provide a solution to the problem of impaired fracture healing. CTM products contain structural proteins, cytokines, and growth factors that may have regenerative and anti-inflammatory properties. Although these products are already used clinically for fracture and wound healing in humans, no pre-clinical studies exist verifying their efficacy or mechanism of action. \u0000Commensal microbiota is a collection of microorganisms such as bacteria, fungi, and viruses.  Disruption of the gut microbiota, known as gut dysbiosis, can lead to a variety of disorders in other tissues. In fact, new studies indicate that alterations in the gut microbiota can affect bone health. This is likely due to impaired nutrient uptake and an increase in inflammation from bacterial byproducts that are not favorable to a healthy gut ecosystem. More recent studies indicate that the microbiota is also implicated in fracture healing. \u0000Our study aims to investigate if CTM products have a positive effect on fracture healing by affecting the gut microbiota composition and bacteriome. To test this, critical sized defects (CSD) were induced in mice and treated with various CTM implants or saline control. Fecal samples were taken on the day of surgery and weekly thereafter. Bacterial DNA was subsequently extracted from these samples and analyzed using PCR. We anticipate seeing changes in load and composition of gut bacteria following CSD surgery.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139626776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of the Binding Partners of Clusterin in their Role in Increased Intraocular Pressure in Glaucoma 分析群集素的结合伙伴在青光眼眼压升高中的作用
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27859
Clay Hepp, Anoop Magesh, Avinash Soundararajan, P. Pattabiraman
{"title":"Analysis of the Binding Partners of Clusterin in their Role in Increased Intraocular Pressure in Glaucoma","authors":"Clay Hepp, Anoop Magesh, Avinash Soundararajan, P. Pattabiraman","doi":"10.18060/27859","DOIUrl":"https://doi.org/10.18060/27859","url":null,"abstract":"Background and Objective:Elevated intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma (POAG). Clusterin (CLU) is a secretory chaperone protein found in trabecular meshwork tissue that is implicated with POAG risk. In this study, we aimed at understanding the role of CLU and its binding partners in IOP homeostasis and POAG pathology. \u0000Methods:Normal trabecular meshwork (NTM) cell lines were used. Half of the NTM cell lines were transfected with adenovirus empty (AdMT) while the other half of the NTM cell lines were transfected with adenovirus clusterin with histidine tag (AdCLUHIS). AdCLUHIS allows for the overexpression of CLU HIS in the NTM cells. After 72 hours of transfection, the media and cell lysate were collected. As CLU is a secretory chaperone protein, the media was analyzed. Immunoprecipitation (IP) was conducted to isolate CLU HIS and all the proteins bound to it. Western blot analysis was conducted to confirmed IP worked successfully. Once it was confirmed that CLU HIS with all its binding partners was isolated successfully using IP, the media samples were sent to proteomics to determine all the specific proteins that are bound directly to CLU. \u0000Results:Western blot analysis confirmed that the overexpression of CLU HIS was successfully accomplished through adenovirus transfection. In addition, Western blot analysis confirmed that IP worked successfully. At the current moment, results of proteomics are still being developed, so the specific binding partners of CLU are still unknown at the time. \u0000Conclusions and Potential Impact:Our preliminary study suggests that CLU can be overexpressed via adenovirus and analyzed via IP. Understanding this allows for the purification of the protein and its attached binding partners. Identifying these binding partners can be novel targets for improving aqueous humor outflow through trabecular meshwork to decrease IOP and decrease one’s risk for POAG.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139626780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Promote Muscle Regeneration in a Diabetic Mouse Model of Critical Limb Threatening Ischemia 诱导多能干细胞衍生的间充质基质细胞促进糖尿病小鼠危重肢体缺血模型中的肌肉再生
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27790
Ali Sualeh, Theresa Doiron, C. Gil, Jennifer Stashevsky, Olivia Jimez, Stone Chen, Nancy Zhang, Humraaz S. Samra, Steven J. Miller, Michael P. Murphy
{"title":"Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Promote Muscle Regeneration in a Diabetic Mouse Model of Critical Limb Threatening Ischemia","authors":"Ali Sualeh, Theresa Doiron, C. Gil, Jennifer Stashevsky, Olivia Jimez, Stone Chen, Nancy Zhang, Humraaz S. Samra, Steven J. Miller, Michael P. Murphy","doi":"10.18060/27790","DOIUrl":"https://doi.org/10.18060/27790","url":null,"abstract":"Critical limb threatening ischemia (CLTI), the end stage of peripheral arterial disease (PAD), is diagnosed in 500,000 patients each year, often results in amputation, and has a ~50% 5-year mortality rate. Diabetic CLTI patients experience especially high morbidity and mortality, and no effective non-surgical therapy exists for this population. Our Phase II MOBILE trial demonstrated that autologous bone marrow nucleated cells were unable to prevent amputations in diabetic patients; however, data from a Phase I trial shows that allogeneic bone marrow-derived mesenchymal stromal cells (BMD-MSC) stimulated angiogenesis in ischemic muscle, including diabetics. While allogeneic MSC may be an effective cell preparation to treat diabetic CLTI, passaging-related cell senescence prevents generation of sufficient cell numbers for therapeutic use. The development of induced pluripotent stem cell (iPSC)-derived MSC overcomes cell senescence issues and offers the possibility of genetic modifications to enhance cell function. The current study was designed to determine potential mechanisms by which iPSC-MSC stimulate muscle regeneration in a rodent CLTI model. \u0000The CLTI mouse model was created by ligation/excision of the femoral artery in male polygenic diabetic TallyHo mice. Mice with intramuscular administration of iPSC-MSC displayed positive indicators of muscle regeneration compared to vehicle control mice. Real-time PCR performed with gastrocnemius muscle obtained 7- or 30-days post iPSC-MSC injection showed an increase in mRNA expression for MyH3, MyoD1, Mrc1, FoxP3, and VEGF-A vs. vehicle treated muscle, indicating promotion of muscle regeneration, M2-biased macrophage expression, T regulatory cell (Treg) expansion, and vascular proliferation. Downregulation of the NADPHoxidase subunit p47phox indicated a decrease in oxidative stress in the treated mice. The results are consistent with iPSC-MSC  promotion of muscle regeneration via a Treg mediated stimulation of the M1-M2 macrophage phenotypic shift. Thus, human iPSC-MSC could be an effective treatment to stimulate muscle regeneration and ameliorate CLTI in diabetic patients.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"43 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139533384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Detection of Bowel and Mesenteric Injuries Using Deep Learning Computer Vision Models 利用深度学习计算机视觉模型检测肠道和肠系膜损伤
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27726
Neal Mahajan, S. Steenburg, Peter Gunderman, John Burns, Arya Iranmanesh
{"title":"Detection of Bowel and Mesenteric Injuries Using Deep Learning Computer Vision Models","authors":"Neal Mahajan, S. Steenburg, Peter Gunderman, John Burns, Arya Iranmanesh","doi":"10.18060/27726","DOIUrl":"https://doi.org/10.18060/27726","url":null,"abstract":"Background/Objective:While only seen in 1-5% of patients who undergo a CT (computed tomography) scan, blunt bowel and mesenteric injuries (BMI) are associated with significantly increased morbidity and mortality. A significant cause of the increased morbidity of BMI is due to the difficulty of diagnosis from clinical and imaging information which leads to delay in diagnosis. Accurate and timely diagnosis is vital to reduce the morbidity of BMI. \u0000Methods:For this project, our primary objective is to create a binary prediction model that determines if a patient has BMI based on their abdominal CT scans. Due to the importance of the early and definitive diagnosis of BMI in trauma patients, an extension of this project will seek to introduce explainability into the model to highlight which features on the CT scan caused the model to make its prediction. The patients with BMI were sourced from a trauma registry that recorded trauma cases from IU Health with relevant diagnosis codes. The images from our search will be reduced to the relevant slices for diagnosis of BMI and then used to train an ML model to makea yes/no prediction from the image. Once the model is trained, testing data will be evaluated on the model and the gradient vectors from the model during inference will be used to create a heatmap with GRAD-CAM that illustrates what portions of the image were relevant for the decision made by the algorithm. \u0000Future Directions:Using the collected abdominal CTs, we can train our machine learning pipeline to detect BMI. Based on the performance of the model, we will determine if we need to collect more data. Then, we can evaluate the explainability of the model using GRAD-CAM and compareperformance of the ML model to the performance of expert and trainee radiologists.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"27 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139534356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-Term Outcomes in Stage II/III Thymic Epithelial Tumor Patients Treated with Post- Operative Radiotherapy 接受术后放疗的 II/III 期胸腺上皮肿瘤患者的长期疗效
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27867
Nikhitha Lavu, Aneesha Anand, Patrick J. Loehrer, Kenneth A. Kesler
{"title":"Long-Term Outcomes in Stage II/III Thymic Epithelial Tumor Patients Treated with Post- Operative Radiotherapy","authors":"Nikhitha Lavu, Aneesha Anand, Patrick J. Loehrer, Kenneth A. Kesler","doi":"10.18060/27867","DOIUrl":"https://doi.org/10.18060/27867","url":null,"abstract":"Thymic epithelial tumors (TETs) are rare malignancies that originate in the anterior mediastinum. Unlike other tumors of the chest, TETs recur most often in the pleura. The primary treatment of early stage TETs is surgical resection, with the role of adjuvant chemotherapy/radiotherapy controversial. Mixed results have been reported as to whether postoperative radiotherapy (PORT) decreases tumor recurrence or time to recurrence, but PORT can cause short-term and long-term toxicity. Therefore, assessing the benefit of PORT is important. For the present retrospective study, we created a database of stage II/III TET patients seen at Simon Cancer Center from 2000-2023 to examine long-term outcomes. Of the 214 stage II/III TET patients that underwent surgery in the database, 67 patients treated with PORT were isolated. Subsequently, 67 patients who did not receive PORT were matched to the PORT population based on similarities in histology, surgical margins, and chemotherapy received. Local vs. distant tumor recurrence, long-term complications, and overall survival were then compared. The PORT population had the following histologic distribution: 3 Type A, 3 Type AB, 47 Type B1/B2/B3, and 14 carcinoma; for the non-PORT population: 8 Type A, 13 Type AB, 36 Type B1/B2/B3, and 10 carcinoma. There were 16 stage IIA, 6 stage IIB, and 45 stage III patients in the PORT population, and 17 stage IIA, 9 stage IIB, and 41 stage III patients in the non-PORT population. The PORT population had 57 recurrences, whereas the non-PORT population had 20 recurrences (p=1.02 x 10-9). The PORT population had 5 deaths and 50 instances of long-term complications, while the non-PORT population had 3 deaths and 25 instances of long-term complications. Overall, these data do not support the routine usage of PORT in resected Stage II/III TET. Further analysis in larger data sets are warranted.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"24 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139534383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE) 青春期前系统性红斑狼疮患者的临床特征
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27814
Ruth Zagales, Stacey E. Tarvin, Martha Rodriguez
{"title":"Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE)","authors":"Ruth Zagales, Stacey E. Tarvin, Martha Rodriguez","doi":"10.18060/27814","DOIUrl":"https://doi.org/10.18060/27814","url":null,"abstract":"Background:\u0000Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organ systems, including cutaneous, renal, neurological, and hematological disorders. Pediatric SLE (pSLE) has a prevalence of 3.3-8.8 cases per 100,000 children. Children with SLE (cSLE) have higher disease severity than adults, but the evidence on cSLE is mostly from pubertal patients, and the reasons for the variation on presentation is unclear. There is limited data on prepubertal SLE, as SLE rarely affects pre-pubescent patients. This study aims to outline the clinical characteristics, disease activity and organ damage of pre-pubescent patients with SLE.\u0000Methods:\u0000A retrospective study was performed on prospectively collected multi-center data from 2005-2015. Patient data, including race, ethnicity, sex, age of presentation and diagnosis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and Systemic Lupus International Collaborating Clinics (SLICC) damage index was collected using REDcap.\u0000Results:\u0000This study included 43 pre-pubescent SLE patients, with an average age at diagnosis of 9.7 years and 10.7 years at the study's start. Organ systems with the highest prevalence rates were musculoskeletal (Arthritis – 69.77%) and cutaneous (Malar rash – 58.14%). The organ systems with the highest involvement frequency, according to the SLICC damage index, were skin (alopecia - 9.3%), ocular (retinal changes/optic atrophy/cataracts - 9.3%), gastrointestinal (pancreatic insufficiency – 4.65%), neuropsychiatric (cognitive impairment – 4.65%), and renal (reduced glomerular filtration rate – 4.65%). Throughout the study, all patients had SLEDAI scores ranging from no activity to high activity, with 55.8% having mild activity, 27.9% having moderate activity, and 14% having high activity.\u0000Conclusion:\u0000Similar to SLE studies on pediatric populations, our study found that cutaneous, gastrointestinal, and renal manifestations were common. However, we found a high prevalence of damage in prepubertal patients, in particular ocular and cognitive impairment. This highlights the need to prioritize ocular exams and cognitive assessments in patients with prepubertal SLE.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"12 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ethanol Induces Blood Brain Barrier Dysfunction in Healthy and Familial Alzheimer’s Blood Brain Barrier Models 乙醇诱导健康和家族性阿尔茨海默氏症血脑屏障模型的血脑屏障功能障碍
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27823
Abby M. Wetzel, Kameron T. Bell, J. Hughes, Scott G. Canfield
{"title":"Ethanol Induces Blood Brain Barrier Dysfunction in Healthy and Familial Alzheimer’s Blood Brain Barrier Models","authors":"Abby M. Wetzel, Kameron T. Bell, J. Hughes, Scott G. Canfield","doi":"10.18060/27823","DOIUrl":"https://doi.org/10.18060/27823","url":null,"abstract":"Background/Objective: \u0000The blood brain barrier (BBB) is a highly selective semipermeable membrane between the blood and brain. Active efflux transporters such as PGP, MRP-1, and BCRP and localized tight junction proteins ensure barrier integrity. Interestingly, both alcohol consumption and Alzheimer’s disease (AD) suppress barrier functions independently. Furthermore, alcohol use can lead to or worsened neurodegenerative disorders, including AD. In this study, human stem-cell derived healthy and AD BBB models with near in vivo properties are used to investigate the effects of alcohol on critical BBB properties such as barrier tightness and efflux transporter activity. \u0000Methods: \u0000Induced pluripotent stem cells (iPSCs) from healthy (IMR90) and Familial Alzheimer’s (APP, PSEN1, PSEN2) cell lines were differentiated into brain microvascular endothelial cells (BMECs).  BMECs were treated with varying ethanol concentrations (5, 25, 50, and 100 mM) for one hour. Following ethanol treatment several barrier properties were assessed: trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, tight junction localization, and efflux transporter activity. \u0000Results: \u0000Moderate to severe ethanol concentrations (25 mM and 50 mM) reduced TEER and delocalized tight junctions in healthy and AD-derived BMECs, indicating a disruption in barrier integrity. AD-derived BMEC cell lines also show an increased susceptibility to ethanol-induced barrier dysregulation at lower concentrations of ethanol (5 mM). Interestingly, our preliminary data shows that ethanol exposure seems to reduce BCRP efflux transporter activity in APP and PSEN1 AD cell lines. \u0000Conclusion and Scientific Impact and Implications: \u0000This study is novel in elucidating the enhanced disruption of BBB properties in familial AD-derived BMEC cell lines following ethanol exposure and provides insight into the potential harm of alcohol consumption in the development and/or exacerbation of BBB dysfunction in Alzheimer’s disease. Further studies will also unveil the possibility of ethanol-induced reduction of BCRP efflux transporter activity in APP and PSEN1 AD.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"9 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of Patient Referrals with Large Numbers of Non-pedunculated Colorectal Lesions 对转诊的大量非梗阻性结直肠病变患者进行评估
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27740
William Cheng, Douglas Rex
{"title":"Assessment of Patient Referrals with Large Numbers of Non-pedunculated Colorectal Lesions","authors":"William Cheng, Douglas Rex","doi":"10.18060/27740","DOIUrl":"https://doi.org/10.18060/27740","url":null,"abstract":"Background: Large (≥20mm) non-pedunculated colorectal lesions are frequently referred to specialty centers for endoscopic resection. These lesions are technically challenging to resectand associated with substantially greater risk than smaller lesions. Patients with such polypsoften have synchronous lesions. We sought to identify evidence for whether synchronouslesions were sometimes the true basis for referral of large non-pedunculated colorectal polypsfrom community endoscopists to a tertiary center. \u0000Methods: We utilized a prospectively collected database of 1356 consecutive referred patients to an expert colonoscopist at our tertiary center between August 2019 and May 2023. We identified patients with ≥30 precancerous lesions resected from the colorectum during their first two colonoscopies at our center. Patients in the database with the same gender, within 3 yearsof age, and with the same location (proximal vs. distal colon) of the index large lesion referred for resection were identified as controls. Groups were compared for the size of index lesion,  number of polyps resected by both centers, and size of polyps resected. \u0000Results: Among 1356 patients, 49 (3.6%) had ≥30 precancerous lesions resected at our center. Compared to controls, the index lesion was smaller in patients with ≥30 lesions (mean 28.9mmvs 23.3mm). Among patients with ≥30 synchronous polyps, the referring physician resected 10.6% of all synchronous lesions, compared to 47.8% in the control group (p<0.0001). Inpatients with ≥30 lesions, 84% of all synchronous lesions were <10mm, 15% were 10-19mm, and only 1% were >20mm. \u0000Conclusion: Our results suggest a subset of patients with large non-pedunculated colorectal precancerous lesions referred to tertiary centers are referred because of the number of lesions present, rather than technical challenges associated with resection of individual lesions. The rationale for these referrals is uncertain. It may lie in the reimbursement system, which only compensates physicians for the first polypectomy.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"27 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139534357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Influence of tGLI-1 on Temozolomide Resistance in Glioblastomas: Unraveling Novel Therapeutic Targets 探索替莫唑胺对胶质母细胞瘤耐药性的影响:揭示新的治疗靶点
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27907
Hannah Von Werder, Haddie DeHart, Richard Carpenter
{"title":"Exploring the Influence of tGLI-1 on Temozolomide Resistance in Glioblastomas: Unraveling Novel Therapeutic Targets","authors":"Hannah Von Werder, Haddie DeHart, Richard Carpenter","doi":"10.18060/27907","DOIUrl":"https://doi.org/10.18060/27907","url":null,"abstract":"Background/Objective:Temozolomide (TMZ) is a standard chemotherapy treatment for patients with glioblastoma (GBM), but its effectiveness is limited, with only 50% of patients initially responding and developing resistance over time. Glioma stem cells (GSCs) have been implicated in TMZ resistance, particularly the mesenchymal subtype. The truncated form of GLI1, known as tGLI1, is highly expressed in mesenchymal GSCs and has been associated with poor patient outcomes in GBM. However, the role of tGLI1 in TMZ resistance remains unknown. \u0000Methods:The GBM cell line, U87MG, was utilized for this study. The IC50 of TMZ was determined using a cell viability assay. After successful transfection with vector, GLI1, and tGLI1, the cells were treated with the IC50 of TMZ to assess changes in cell viability between the groups. \u0000Results:The IC50 of TMZ is 290.1 μM, as averaged between replicate assays. Thus far, the results showed that tGLI1-expressing cells exhibited significantly higher cell viability (average: 39.09%) compared to Vector (average: 26.78%) and GLI1 (average: 27.11%). However, the tGLI1 group displayed higher variability in cell viability results, as evidenced by a larger standard deviation (0.2758) and standard error (0.1592) compared to vector (SD: 0.0325, SE: 0.0188) and GLI1 (SD: 0.1354, SE: 0.0781). The One-Way ANOVA, followed by Tukey's Multiple Comparison Test, results showed no statistically significant differences in cell viability between the groups. \u0000Conclusion/Impact:The increased cell viability observed in tGLI1-expressing cells suggests a potential association between tGLI1 and TMZ resistance, warranting additional research to fully comprehend its impact on GBM treatment response. Further investigation and replication studies are needed to establish the robustness of these results. This knowledge may contribute to the development oftargeted therapies aimed at inhibiting tGLI1 or its downstream signaling pathways, potentiallyimproving the response to TMZ and patient outcomes.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"2 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinician Perspectives on Risks and Benefits of Sharing Cardiovascular Implanted Electronic Device (CIED) Data with Patients 临床医生对与患者共享心血管植入式电子设备 (CIED) 数据的风险和益处的看法
Proceedings of IMPRS Pub Date : 2024-01-11 DOI: 10.18060/27805
Brandon Tran, Carly Daley, Stephanie Pruitt, Jonathan Shirazi, Tina Allmandinger, Tammy R Toscos, Michael Mirro
{"title":"Clinician Perspectives on Risks and Benefits of Sharing Cardiovascular Implanted Electronic Device (CIED) Data with Patients","authors":"Brandon Tran, Carly Daley, Stephanie Pruitt, Jonathan Shirazi, Tina Allmandinger, Tammy R Toscos, Michael Mirro","doi":"10.18060/27805","DOIUrl":"https://doi.org/10.18060/27805","url":null,"abstract":"Background and Objective: Cardiovascular implantable electronic devices (CIEDs) are critical, life-saving devices that are essential for the clinical decision-making process due to the data they collect. Because not all patients have ready access to their device data, there may be a clinical care gap where the CIED data are not being used most effectively in the care of patients with CIEDs. However, sharing CIED data may risk harming clinician-patient relationships and necessitates further study into clinician’s perspectives on CIED data sharing. The objective of this study was to explore clinicians’ perspectives on sharing CIED data with their patients and explore the perceived benefits and concerns. \u0000Methods: Clinicians involved in CIED care in the United States were recruited for semi-structured phone interviews. Participants were asked questions regarding their experiences and perspectives in sharing CIED data, and were presented scenarios to assess how they would leverage the CIED data in particular situations. Responses from the participants were analyzed by one researcher using thematic analysis. \u0000Results: Of the 28 clinicians interviewed in this study, the majority were white (85.7%) and located in the midwestern United States (67.9%). Participants included cardiac device clinic nurses and electrophysiology nurses (28.6%), electrophysiologists (25%), electrophysiology advanced practice providers (APPs) (17.9%), cardiologists (14.3%), and cardiology APPs (14.3%). The following themes were identified: (1) Patient engagement with healthcare, (2) Patient selfadvocacy, (3) Patients cannot interpret CIED data, (4) One size does not fit all. \u0000Conclusion and Potential Impact: Clinicians perceived both potential benefits and harms from CIED data sharing. Clinicians noted that CIED data sharing has the potential to increase patient participation in their healthcare, but it also can cause increased patient anxiety due to insufficient patient education. This study demonstrated some of the ways CIED data sharing may affect clinical practice involving CIEDs and the challenge of sharing complex data elements with patients.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"6 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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