tbuckley/cabot-search huggingface dataset:
The Impact of Cholangioscope Diameter Variation on Cholangioscopy Outcomes: A Retrospective Comparative Study
Authors: C. Robles-Medranda, J. Baquerizo-Burgos, M. Puga-Tejada, J. Alcivar-Vasquez, R. Del Valle, H. Alvarado-Escobar, M. Egas-Izquierdo, D. Cunto, M. Arevalo-Mora, H. Pitanga-Lukashok
Journal: Endoscopy (2024)

Aims Digital single-operator cholangioscopy (DSOC) stands as an invaluable diagnostic and therapeutic instrument, offering direct visualization of the biliary ducts. The use of cholangioscopes with higher diameter may raise concerns regarding patient discomfort and safety. Smaller diameter cholangioscopes could offer enhanced maneuverability and decreased risk of adverse events, improving procedural success rates. The aim of this study is to compare the impact of cholangioscope diameter variation on cholangioscopy outcomes, with a focus on procedure success rates.
Combined treatment of T1 rectal cancer in patient with comorbidities. Endoscopic mucosal resection and endoscopic full-thickness resection of scar
Authors: J. A. Núñez-Otero, J. L. Larrea-Yanez, A. Díaz-Sánchez, E. Moya-Valverde, R. Manzano-Fernández, A. I. González-Tallón, S. García-Mulas, M. Martin-Matas, L. Diéguez-Montes, M. Rivero-Fernández
Journal: Endoscopy (2024)

Abstract Text A 81-year-old male with comorbidities, was referred for rectal bleeding. Colonoscopy: in rectum, a 20 mm sessile lesion with a high risk of adenocarcinoma (non-granular LST, Kudo pattern Vi-Vn). Stage T1,N0 by MRI and EUS. Given the age and comorbidity surgery was ruled out and endoscopic full-thickness resection (eFTR) was offered. Firstly, assessed with a test cap, being very friable when picked up with forceps, tearing easily, which makes it impossible to insert it inside the cap. In bloc endoscopic mucosal resection (EMR) is performed first, and subsequently, eFTR is realized. Histology: infiltrating adenocarcinoma moderately differentiated (G2) submucosal invasion without lymphovascular or perineural involvement. Scar without malignancy. No recurrences were detected during follow-up.The combination of EMR and eFTR of the scar in the same procedure can be an alternative in selected cases.
Endoscopic Papillectomy : A single center 4-year retrospective study
Authors: X. Tsamakidis, D. Kypraios, A. Kontos, N. Sarimpegioglou, G. Sachtouris, P. Ippokratis, I. Marakis, E. Manthopoulou, S. Stavrinidis, E. Michalopoulou, F. Papakonstantinou, V. Giannakopoulos, I. Tziortziotis, M. Al-Ountat, D. Dimitroulopoulos
Journal: Endoscopy (2024)

Aims Endoscopic papillectomy has been established as the treatment of choice for ampullary adenomas provided that certain criteria are met. Nevertheless, the evaluation studies are limited in international literature. The aim of the present study is to evaluate the efficacy and safety of this technique as long as the long-term outcomes.
Descriptive Analysis of characteristics of patients that have undergone small bowel capsule endoscopy
Authors: A. Tsakou, N. Lazaridis, S. Tsiamitros, G. Kalopitas, G. Germanidis
Journal: Endoscopy (2024)

Aims The use of Small Bowel Capsule Endoscopy (SBCE) is recommended in patients with suspected small bowel bleeding (SSBB), overt suspected small bowel bleeding, iron deficiency anemia and suspected Crohn disease with a prior negative upper endoscopy and ileocolonoscopy. In comparison to other diagnostic modalities of small bowel examination, its use is simple, safe, and has a great diagnostic yield. The aim of this study is to analyse the characteristics of patients that have undergone SBCE.
The outpatient management in gastrointestinal bleeding reduces the re-bleeding during the time: a cohort observational study
Authors: C. Marmo, D. Feliciani, B. Funaro, L. Petrucci, A. Gasbarrini, M. E. Riccioni
Journal: Endoscopy (2024)

Aims The aim of the study is to verify if the outpatient management of patients with gastrointestinal bleeding from vascular lesions reduces the re-bleeding rate
Factors of good response to endoscopic dilatation in Plummer Vinson Syndrome
Authors: H. Cherkaoui, A. El Ghmari, E. M. Amine, N. Lahmidani, D. A. Benajah, E. Y. Mounia, S. A. Ibrahimi, M. El Abkari, H. Abid
Journal: Endoscopy (2024)

Aims Plummer-Vinson syndrome (PVS) is a rare disease that occurs mainly in young women. It consists of an upper dysphagia with iron deficiency anemia and a ring in the cervical esophagus on upper gastrointestinal endoscopy. Our work aims to determine the results of endoscopic dilatation in our series and the number of dilation sessions needed to achieve satisfactory clinical results.
Design and applications of a simulator based on the morphology of an actual stomach for training in endoscopic therapy
Authors: J. Zhang, Q. Guo, Q. Zheng, T. Qiuyue, X. Zhang, M. Shi, D. Liu, B. Liu
Journal: Endoscopy (2024)

Aims At present, many different types of endoscopic trainers are not constructed according to the actual gastric morphology. Therefore, we have developed a new simulator for endoscopic therapy technology, evaluated its efficacy and authenticity in endoscopic operation, and explored the learning curve of novice endoscopic physicians and the training effect.
Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membrane-decorated nanoparticles
Authors: Wen Zhang, Yihui Zhai, Ying Cai, Xiang Gong, Yunxuan Jiang, Rong Rong, Chao Zheng, Binyu Zhu, Helen He Zhu, Hao Wang, Yaping Li, Pengcheng Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Current cytotoxic T lymphocyte (CTL) activating immunotherapy requires a major histocompatibility complex I (MHC-I)-mediated presentation of tumor-associated antigens, which malfunctions in around half of patients with triple-negative breast cancer (TNBC). Here, we create a LCL161-loaded macrophage membrane decorated nanoparticle (LMN) for immunotherapy of MHC-I-deficient TNBC. SIRPα on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161, which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells. The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds. LMNs also block CD47-mediated phagocytosis suppression. LMNs inhibit the growth of MHC-I-deficient TNBC tumors, as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel, and prolong the survival of animals, during which process CTLs also play important roles. This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.
(Re-)introduction of TNF antagonists and JAK inhibitors in patients with previous tuberculosis: a systematic review
Authors: Thomas Theo Brehm, Maja Reimann, Niklas Köhler, Christoph Lange
Journal: Clinical Microbiology and Infection (2024)

Tuberculosis (TB) is a common complication associated with treatment with tumour necrosis factor (TNF) antagonists and Janus kinase (JAK) inhibitors. However, there is uncertainty about the risk of TB relapse in patients with TB and comorbidities requiring treatment with these agents.
Phenylalanine deprivation inhibits multiple myeloma progression by perturbing endoplasmic reticulum homeostasis
Authors: Longhao Cheng, Xiaoxue Wang, Aijun Liu, Ying Zhu, Hu Cheng, Jiangling Yu, Lili Gong, Honglin Liu, Guolin Shen, Lihong Liu
Journal: Acta Pharmaceutica Sinica B (2024)

Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment
Nanoparticle-neutrophils interactions for autoimmune regulation
Authors: Daniel Kupor, Michael L. Felder, Shivanie Kodikalla, Xueqi Chu, Omolola Eniola-Adefeso
Journal: Advanced Drug Delivery Reviews (2024)

Neutrophils play an essential role as 'first responders' in the immune response, necessitating many immune-modulating capabilities. Chronic, unresolved inflammation is heavily implicated in the progression and tissue-degrading effects of autoimmune disease. Neutrophils modulate disease pathogenesis by interacting with the inflammatory and autoreactive cells through effector functions, including signaling, degranulation, and neutrophil extracellular traps (NETs) release. Since the current gold standard systemic glucocorticoid administration has many drawbacks and side effects, targeting neutrophils in autoimmunity provides a new approach to developing therapeutics. Nanoparticles enable targeting of specific cell types and controlled release of a loaded drug cargo. Thus, leveraging nanoparticle properties and interactions with neutrophils provides an exciting new direction toward novel therapies for autoimmune diseases. Additionally, recent work has utilized neutrophil properties to design novel targeted particles for delivery into previously inaccessible areas. Here, we outline nanoparticle-based strategies to modulate neutrophil activity in autoimmunity, including various nanoparticle formulations and neutrophil-derived targeting.
Abstract 14360: Clinical Significance of the Assessment of Valvular Calcification Using <sup>18</sup> F-sodium Fluoride Positron Emission Tomography
Authors: Rie Aoyama, Masashi Kameyama, Joji Ishikawa, Kazumasa Harada
Journal: Circulation (2021)

Introduction: With an aging population, valvular heart disease (VHD) of a degenerative etiology has been increasing. Although calcification of valves and mitral annulus (MAC) increase in the elderly, these calcification lesions are considered as one of the causes of embolic stroke of undetermined source (ESUS). On the other hand, it is difficult to evaluate the instability of calcification using echocardiology or CT and to clarify the relationship between the instability of calcification and the onset of cerebral infarction. 18 F-Sodium Fluoride ( 18 F-NaF) is a Positron Emission Tomography (PET) tracer acts as a marker of newly developing calcium in the cardiovascular system. Therefore, we evaluated the qualitative evaluation of calcification lesions using NAF and the onset of cerebral infarction. Methods/Results: One hundred and twenty-five preoperative orthopedic patients (78.0±6.3 years old, 13 male) underwent 18 F-NaF-PET/CT and echocardiography between February 2015 and March 2019 and the accumulation was analyzed in each calcification. MAC was admitted in 46 patients, Aortic valve calcification was in 22 patients, and Mitral valve calcification was in 48 patients. The accumulation of 18 F-NaF on calcified lesions was admitted in 41, 33, 48 patients, each. History or new onset of cerebral infarction was in 14 patients, and among them 13 patients (92.9%) had the accumulation of 18 F-NaF on calcified lesions. Calcification with the accumulation of 18 F-NaF was correlated with cerebral infarction (p&lt;0.01 by chi-square) and the uptake grade of 18 F-NaF on calcification was linearly correlated with the onset of cerebral infarction. Conclusions: The accumulation of 18 F-NaF may predict the instability of calcification and the risk of cerebral infarction.
Abstract 14366: Pulmonary Hypertension-Induced RV Hypertrophy and Dysfunction is Associated With Reduced Activity and Abundance of Complex IV in Respiratory Supercomplexes
Authors: Wenzhuo Ma, Alexander Vang, Scarlett Huck, Thomas Mancini, Preston Nicely, Peng Zhang, Gaurav Choudhary, Richard T Clements
Journal: Circulation (2021)

Introduction: PH results in RV hypertrophy, fibrosis and impaired function resulting in RV failure. PH is associated with impaired heart metabolism and mitochondrial respiration. Mitochondrial supercomplexes (mSC) are assemblies of multiple electron transport chain (ETC) complexes that consist of physically associated complex I, III and IV to enhance respiration. We determined if activity and/or abundance of mSC’s is altered in a rat model of PH. Methods: PH was induced in SD-rats by Sugen-Hypoxia (3 weeks) followed by normoxia (4 weeks) . Control (n=11) and PH (n=10) were subjected to echocardiography and isolation of LV and RV mitochondria. Clear native PAGE with equal amounts mitochondrial protein was used for SC abundance and activity with immunoblot or in gel activity with specific substrates. Results: PH animals had significantly reduced PAT and TAPSE, increased RV wall thickness and hypertrophy (RV/LVS). Western analysis of total protein fractions demonstrated reductions in representative CI, II, III, and IV proteins in RV indicating reduced mitochondrial content in PH. Assays with normalized mitochondrial protein showed activity (100+/- 3.6 vs 64.0+/-3.8 %, p&lt;.01) and abundance (100+/-1.8 vs 49.3 +/-1.1, p=.02) of complex IV in mitochondrial SCs was severely reduced in PH animals compared to control. There were no differences in total CIV activity or abundance in lower order ETC assemblies (100 vs 97.5%, p=.78). TAPSE, PAT and RV Wall thickness significantly correlated with CIV SC activity (r=.71, .66, and -.80 respectively P&lt;.01). CIII abundance was lower in SCs (P=.01) but total CIII unchanged. CI activity in SC assemblies was reduced in PH but this was not significant (100+/-12 vs 77.4 +/-8.2, p=.14). Overall levels of CI were unchanged. There were no changes in CII activity or abundance in RV or LV. In the LV, activity of CIV in SC was reduced in PH (100+/-6 vs 78+/-6, p=.02) but to a lesser extent than RV. There were also decreases in overall abundance of CIII and CIV assemblies in the LV in PH. Conclusion: The data support the concept that although mitochondrial abundance may be altered, there are also significant alterations associated with assembly and activity of mitochondrial SCs in the RV with pronounced differences in complex IV assembled into SCs.
Abstract 14413: Genetic Deletion of Cardiomyocyte Glutamine Synthetase in a Model of HF Hints at Cardiomyocyte to Fibroblast Metabolic Crosstalk Mediating Fibrosis
Authors: Andrew A Gibb, Tori Ploesch, Zoltan Arany, John W Elrod
Journal: Circulation (2021)

Introduction: Recent evidence in heart failure patients revealed a significant release of glutamine from the heart as evidenced by arterial-coronary sinus concentration differences. Interestingly, enhanced glutamine utilization is required for fibroblast to myofibroblast differentiation and persistence in response to stress stimuli. Therefore, the aim of this study was to determine if cardiomyocyte-derived glutamine influences fibroblast activation and fibrosis. Methods: To determine the effects of cardiomyocyte glutamine production in the failing heart, glutamine synthetase floxed mice (GS fl/fl ) were bred with the cardiomyocyte-specific, tamoxifen-activated Cre mice (MCM). (GS catalyzes the condensation of glutamate to glutamine.) GS fl/fl x MCM and MCM controls were fed tamoxifen chow for 1w followed by a 1w washout. Western blotting confirmed cardiomyocyte GS deletion and baseline LV function was assessed by echocardiography, followed by randomization to sham or TAC surgery. Cardiac function was tracked at 4, 8, and 12wks post-TAC followed by tissue collection, assessment of gravimetrics, and histological staining. Results: Cardiomyocytes isolated from GS fl/fl x MCM hearts following tamoxifen administration revealed a near complete loss of GS protein. While loss of GS did not impact baseline cardiac function, GS fl/fl x MCM mice were significantly protected against pressure-overload induced cardiac dysfunction indicated by preserved FS% (n=8/group; p&lt;0.0001) and decreased LVESD (n=8/group; p=0.001). Deletion of cardiomyocyte GS did not appreciably impact hypertrophy. To ascertain if the fibrotic response was altered, we performed picrosirius red staining 12w following TAC. Hearts from GS fl/fl x MCM mice showed an ~3-fold reduction in total cardiac fibrosis, as compared to MCM controls. (n=6/group; p=0.01). Conclusions: Our results suggest that cardiomyocyte glutamine synthesis may play a significant role in fibroblast activation and fibrosis in heart failure. Studies are currently underway to identify the precise mechanisms governing metabolic cardiomyocyte to fibroblast crosstalk.
Abstract 14436: Effects of Uncertainty in Border Delineation on GLS <sub>BL</sub> versus LVEF
Authors: Walter ODell, Shoba Abraham, Daniela Lucas, Shruti Siva Kumar
Journal: Circulation (2021)

Background: There are many clinical scenarios in which early detection of small changes in cardiac function can be critical in determining a patient’s treatment. Two of the most common imaging-based metrics in the clinic are LVEF and border-length-based GLS (GLS BL ). The aim of this project was to analyze the inherent biases and uncertainties in GLS BL relative to LVEF with respect to uncertainties in delineation of the endocardial border. Methods: I n silico 3D human LV endocardial surface models were created at end-diastole and end-systole based on MRIs of a healthy human volunteer. Twelve virtual long-axis imaging slices (in a radially-prescribed) were projected through the surface models to generate noise-free endocardial contour points. To simulate border delineation uncertainty, the set of endocardial contour points was subjected to inward and outward shifts of 1-5 mm, incrementally (Fig 1A). The expected uncertainty when using EC is around 3 mm. The % error vs. offsets were calculated for bi-plane GLS BL , bi-plane area-length LVEF AL , and bi-plane method-of-disks LVEF MOD , with 3D conformal surface-fit LVEF SURF as ground-truth. Results: The GLS BL %error vs. offset was linear (R 2 = 1.000) with a slope of 4.92 (Fig. 1B). Each of the LVEF measures were quadratic with offset (R 2 = 1.000), with slopes: LVEF AL : 6.68; LVEF MOD : 6.71; and LVEF SURF : 10.26. Conclusions: GLS BL is less sensitive to boundary delineation uncertainty than LVEF, due to the linear vs. quadratic dependence on offset. LVEF AL and LVEF MOD consistently underestimate true LVEF, making them less sensitive to boundary uncertainty. However, if border uncertainty is negligible, then LVEF is more sensitive than GLS BL to small changes in LV volume, and LVEF SURF is more sensitive than either LVEF AL and LVEF MOD .
Abstract 14382: Association of Atherosclerotic Plaque Burden and FFR <sub>CT-</sub> Serial Cardiac CTA Study
Authors: Kashif Shaikh, April Kinninger, Suraj Dahal, Suvasini Lakshmanan, Ilana Golub, VENKATA M ALLA, Jonathon Leipsic, Matthew Budoff
Journal: Circulation (2021)

Introduction: Cross-sectional studies have shown the association of atherosclerotic plaque burden and FFR CT . However, the relationship between changes in anatomic CCTA parameters and FFR CT has not been evaluated. In the present study, we sought to study the natural history of FFR CT and to observe the impact of coronary plaque characteristics on intracoronary hemodynamics over time as assessed by noninvasive CCTA. Methods: Patients who had undergone baseline and follow-up CCTA were included. Coronary plaque scores and vessel stenosis severity were quantified on CCTA. Multivariate linear regression was used to examine the association of change in the per vessel FFR CT , average distal FFR CT, and the most diseased vessel FFR CT with total plaque score(TPS), coronary artery calcium(CAC), total segment stenosis (TSS), segment involvement score (SIS). Results: Final analysis included 101 subjects (83% male; age 65.5 ± 10.1 years). After adjusting for several cardiovascular risk factors, on a per-vessel basis involving the most significant lesion, a 1 unit increase in TPS resulted on average in a 0.008 decrease in FFR in the most diseased vessel, p=0.004, after adjusting for several risk factors. Using the average FFR CT of the distal LAD, RCA, and LCX, a 1 unit increase in TPS results on average in a 0.004 decrease in the distal average FFR, p=0.026. A 1 unit increase in TPS results on average in 0.005 decrease in the RCA distal pins of FFR, p=0.033 (Table 1). There are no significant associations of the LCX and LAD FFR with TPS. There are no significant associations of the change in FFR CT with TSS, SIS or CAC progression. Conclusion: Worsening atherosclerotic plaque burden is associated with worsening physiology as assessed on CCTA as assessed by FFR CT . Therapies that stabilize or regress plaque may improve overall physiology. Further prospective trials are required to validate these findings.
Abstract 9872: Cardiac Enhancer Variants at the <i>Mtss1</i> Locus Are Associated with Smaller, More Contractile Hearts
Authors: Megan F Burke, Michael P Morley, Yifan Yang, Theodore G Drivas, dongwook choe, Sharlene Day, Kiran Musunuru, Mingyao Li, Marylyn Ritchie, Thomas P Cappola
Journal: Circulation (2021)

Introduction: Variants at the MTSS1 locus influence cardiac structure, function, and failure in multiple genome wide association studies (GWAS), yet the genetic mechanisms remain unclear. We previously identified variants in a cardiac enhancer in cis to MTSS1 that influence expression in the human left ventricle (LV). Here we used bioinformatic approaches to determine if these variants explain the association between common MTSS1 variation and cardiac traits. We hypothesized that alleles that reduce MTSS1 expression are cardioprotective. Methods: To confirm a shared causal variant, we combined expression quantitative trait locus (eQTL) data from GTEx with GWAS from the UKBiobank (UKBB) using co-localization. GTEx consists of 386 LV samples with RNAseq. The UKBB is a prospective study of over 500,000 patients recruited from the United Kingdom with extensive genotype and phenotype data. We obtained relevant data as part of approved protocol 65965, using 82 additional quantified cardiac MRI (cMRI) traits from return dataset 2383. Genome association tests were performed at the MTSS1 locus (chr8:124550790-124728429) using Plink2.0; co-localization was performed with Coloc. Results: Co-localization analysis of 26,892 patients revealed 3 overlapping variants in the MTSS1 enhancer region significantly associated with LV expression of MTSS1 and multiple cMRI traits. These include LV ejection fraction (LVEF) (p=1.3 x 10 -10 ), LV end-systolic volume (p=1.2 x 10 -8 ), and global circumferential strain (p=1.1 x 10 -7 ). Variants that decrease MTSS1 expression are associated with decreased volumes, increased LVEF, and improved circumferential strain, consistent with smaller, more contractile hearts (see figure for detail). Conclusion: We utilize a bioinformatics approach to clarify genetic mechanisms by which a previously identified locus modulates cardiac traits. These results support a cardioprotective phenotype associated with reduced LV MTSS1 expression.