tbuckley/cabot-search huggingface dataset:
SLFN5 Regulates LAT1-Mediated mTOR Activation in Castration-Resistant Prostate Cancer
Authors: Rafael S. Martinez, Mark J. Salji, Linda Rushworth, Chara Ntala, Giovanny Rodriguez Blanco, Ann Hedley, William Clark, Paul Peixoto, Eric Hervouet, Elodie Renaude, Sonia H.Y. Kung, Laura C.A. Galbraith, Colin Nixon, Sergio Lilla, Gillian M. MacKay, Ladan Fazli, Luke Gaughan, David Sumpton, Martin E. Gleave, Sara Zanivan, Arnaud Blomme, Hing Y. Leung
Journal: Cancer Research (2021)

Abstract Androgen deprivation therapy (ADT) is the standard of care for treatment of nonresectable prostate cancer. Despite high treatment efficiency, most patients ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we performed a comparative proteomic analysis of three in vivo, androgen receptor (AR)-responsive orthograft models of matched hormone-naïve prostate cancer and CRPC. Differential proteomic analysis revealed that distinct molecular mechanisms, including amino acid (AA) and fatty acid metabolism, are involved in the response to ADT in the different models. Despite this heterogeneity, Schlafen family member 5 (SLFN5) was identified as an AR-regulated protein in CRPC. SLFN5 expression was high in CRPC tumors and correlated with poor patient outcome. In vivo, SLFN5 depletion strongly impaired tumor growth in castrated conditions. Mechanistically, SLFN5 interacted with ATF4 and regulated the expression of LAT1, an essential AA transporter. Consequently, SLFN5 depletion in CRPC cells decreased intracellular levels of essential AA and impaired mTORC1 signaling in a LAT1-dependent manner. These results confirm that these orthograft models recapitulate the high degree of heterogeneity observed in patients with CRPC and further highlight SLFN5 as a clinically relevant target for CRPC. Significance: This study identifies SLFN5 as a novel regulator of the LAT1 amino acid transporter and an essential contributor to mTORC1 activity in castration-resistant prostate cancer.
Copper single-atom catalysts with photothermal performance and enhanced nanozyme activity for bacteria‐infected wound therapy
Authors: Xianwen Wang, Qianqian Shi, Zhengbao Zha, Dongdong Zhu, Lirong Zheng, Luoxiang Shi, Xianwen Wei, Lian Lian, Konglin Wu, Liang Cheng
Journal: Bioactive Materials (2021)

Nanozymes have become a new generation of antibiotics with exciting broad-spectrum antibacterial properties and negligible biological toxicity. However, their inherent low catalytic activity limits their antibacterial properties. Herein, Cu single-atom sites/N doped porous carbon (Cu SASs/NPC) is successfully constructed for photothermal-catalytic antibacterial treatment by a pyrolysis-etching-adsorption-pyrolysis (PEAP) strategy. Cu SASs/NPC have stronger peroxidase-like catalytic activity, glutathione (GSH)-depleting function, and photothermal property compared with non-Cu-doped NPC, indicating that Cu doping significantly improves the catalytic performance of nanozymes. Cu SASs/NPC can effectively induce peroxidase-like activity in the presence of H
Abstract 13334: Cardio-ankle Vascular Index Reflects Impaired Exercise Capacity and Predicts Adverse Prognosis in Patients With Heart Failure
Authors: Koichiro Watanabe, Akiomi YOSHIHISA, Yu Sato, Yu Hotsuki, Yasuhiro Ichijo, Yusuke KIMISHIMA, Tetsuro Yokokawa, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Yasuchika Takeishi
Journal: Circulation (2020)

Aims: We aimed to clarify the associations of cardio-ankle vascular index (CAVI) with exercise capacity and prognosis in patients with heart failure (HF). Methods and Results: We recruited clinical data of total of 273 patients hospitalized for treatment of decompensated HF, and underwent both CAVI and cardiopulmonary exercise testing at stable condition in prior to hospital discharge. For the prediction of impaired peak oxygen uptake (VO 2 ) of &lt; 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. According to the multiple logistic regression analysis, high CAVI was independently associated with impaired peak VO 2 (odds ratio 2.055, 95% confidence interval 1.015-3.960, P = 0.045). We divided these patients based on CAVI: the low CAVI group (CAVI &lt; 8.9, n = 178, 65.2%) and the high CAVI group (CAVI ≥ 8.9, n = 95, 34.8%). We compared the patients’ characteristics and cardiac events such as cardiac death and re-hospitalization due to worsening HF between the two groups. The high CAVI group was older (69.0 vs. 58.0 years old, P &lt; 0.001) and showed lower body mass index (22.9 vs. 23.8 kg/m 2 , P = 0.018). With respect to laboratory data, levels of estimated glomerular filtration rate were lower in the high CAVI group than in the low CAVI group (56.1 vs. 64.2 mL/min/1.73 m 2 , P = 0.001). During the post-discharge follow-up period of median 1,544 days, 76 cardiac events occurred. The Kaplan-Meier analysis showed that cardiac event rates was higher in the high CAVI group than in the low CAVI group ( Figure , Log-rank P = 0.021). In the multivariable Cox proportional hazard analysis, high CAVI was found to be an independent predictor of cardiac events (hazard ratio 1.765, 95% confidence interval 1.123-2.773, P = 0.014). Conclusions: High CAVI independently associated with impaired exercise capacity accompanied by a high cardiac event rate in HF patients.
만성 B형간염 환자에서 항바이러스치료 방법들의 비용-효과 분석
Authors: 김병국 ( Byung Kook Kim ), 권소영 ( So Young Kwon ), 이창홍 ( Chang Hong Lee ), 최원혁 ( Won Hyeok Choe ), 최홍미 ( Hong Mi Choi ), 구혜원 ( Hye Won Koo )
Journal: Clinical and Molecular Hepatology (2009)

목적: 본 연구의 목적은 CHB에 대한 단기간 치료와 5년까지 장기간 항바이러스치료에 대한 비용-효과를 평가하고자 하였다. 대상과 방법: 두 개의 10-health state Markov 모델을 각각 HBeAg 양성과 HBeAg 음성 CHB 환자들에 대하여 적용하였다. 모델은 HBeAg 양성과 음성 CHB 환자의 코호트를 모델로 치료를 받지 않았다면 코호트의 대부분이 사망했을 시기인 40년 이상의 기간 동안 추적하였다. 질병의 연간 진행률과 치료 효과에 대한 정보는 아시아 환자에서 얻은 자료들이나 국제적으로 알려진 치료지침에 기술된 기준에 합당한 문헌들을 토대로 수집하였다. 다양한 항바이러스치료 방법들에서 비용-효과를 분석하였다. 결과: 단기간 IFN이나, 1년간의 PEG-IFN, LMV 또는 ADV 치료는 질병의 진행에 대한 효과가 제한적이었다. 이에 반하여, 5년간의 LMV-ADV 치료나, ADV-LMV 치료는 치료 기간 동안 질병의 진행률을 감소시킬 수 있었다. 삶의 질로 보정된 생존년에 대한 점증적 비용-효과 비(ICER)의 임계값은 대략 25,000,000원이 될 것으로 추정하였다. HBeAg 양성과 HBeAg 음성 CHB 환자 모두 1년간 LMV을 사용하는 것이 치료를 받지 않은 것에 비하여 비용에 대한 효과가 크지만, 질병진행률을 감소시키는 데는 제한적인 효과를 보였다. LMV으로 1년간 CHB을 치료하는 것과 비교하여 5년까지 LMV-ADV 또는 ADV-LMV의 장기간 항바이러스제 치료는 HBeAg 양성과 음성 CHB 모두에서 기준에 비하여 비용-효과가 매우 우수하였다. LMV-ADV 치료에서 QLAY당 비용은 HBeAg 양성의 경우 8,067,125원, HBeAg 음성인 경우 4,777,458원 그리고 ADV-LMV 치료에서는 각각 15,965,817원, 8,372,415원으로 국제 비용-효과 비의 임계 값보다 낮았다. 결론: 현재까지 우리나라 CHB 환자에서 장기간의 LMV-ADV 치료는 비교적 비용-효과적인 방법이며 질병의 진행률을 감소시킴으로써 의료비용을 낮출 수 있을 것으로 예상할 수 있다. 최근에 사용되고 있는 새로운 항바이러스제들의 장단기 효과를 반영한 우리나라 실정에 맞는 항바이러스치료의 경제성 평가 연구가 필요하다.
Abstract P154: Leisure-Time Physical Activity, Sedentary Behavior, And Carotid Atherosclerosis Morphology: The ARIC Carotid-MRI Study
Authors: Aarti Kumar, Ye Qiao, Bruce Wasserman, Kelley P Gabriel, Keith Diaz, Kelly R Evenson, Aaron R Folsom, A Richey Sharrett, Yiyi Zhang, Gerardo M Heiss, Priya Palta
Journal: Circulation (2021)

Introduction: Studies suggest that greater physical activity (PA) may be associated with favorable carotid artery characteristics, while greater time spent in sedentary behavior (SB) may be a potential risk factor for atherosclerosis development and progression. We evaluated the association between leisure-time PA and SB in midlife and their temporal patterns with carotid atherosclerotic morphology measured by MRI. Methods: ARIC Carotid-MRI participants (n=1582, mean age: 53 years, 43% male, 18% Black) with self-reported assessments of PA and SB at visits 1 (1987-1989) and 3 (1993-1995), who participated in the Carotid MRI substudy in 2004-2006 were included. Self-reported leisure-time PA was categorized based on the American Heart Association’s Life Simple 7 categorization of ideal, intermediate, or poor PA. SB was ascertained based on participant report of how often they watched television during leisure-time, and categorized as low [“never”/ “seldom”], medium [“sometimes”], or high [“often”/“very often”]. To measure persistent PA and SB, we examined participants who reported the same level of PA (n=849) or SB (n=954) at both visits 1 and 3. Carotid MRI using a 1.5T scanner quantified internal carotid artery wall thickness, lipid core, and calcification measures. Weighted analyses accounted for the sampling design allowing for generalizability to the visit 1 ARIC population. Multivariable linear and logistic regression were used for continuous and categorical outcomes, respectively. All models were adjusted for demographic, behavioral, and lifestyle factors. Results: Though no clear trends were observed for PA, higher levels of SB were associated with a greater odds of lipid core presence and lower odds of calcification (Table). Similar trends were observed for the persistence analyses, though none were statistically significant. Conclusions: PA and SB may influence atherosclerotic plaque characteristics. SB and lack of PA may have different measurable effects on plaque morphology.
Multimarker assay for early diagnosis of ovarian cancer
Authors: Anna E. Lokshin, Zoya Yurkovetsky, Brian Nolen, Adele M. Marrangoni, Lydmila Velikokhatnaya, Andrzej Drukier, Steven Skates, Elieser Gorelik
Journal: Cancer Research (2006)

653  Clinical outcome of ovarian cancer patients may be improved by early detection. We hypothesized that a panel comprised of multiple ovarian cancer-associated biomarkers may yield a better diagnostic tool than each individual marker. We utilized the same novel multiplexing LapMAP™ technology that allowed us to evaluate the large panel of biomarkers that have previously shown correlation with epithelial cancers. Concentrations of 46 biomarkers, cancer antigens, CA 125, CEA, CA 15-3, AFP, CA19-9, CA 72-4; growth/angiogenic factors, VEGF, bFGF, EGF, IGFBPI, HGF ErbB2, EGFR; apoptosis-related molecules, Fas, FasL, CK19; metastasis-related molecules, MMP-2, MMP-3, MMP-7, tPAI, sICAM, V-CAM, sE-selectin; Cytokines, IL-6, IL-8, G-CSF, IP-10, MCP-1, MIP-1a, MIP-1b MIF, IL-2R, Eotaxin; hormones, bHCG, FSH, LH, GH, TSH, ACH, and prolactin; kallikreins 8 and 11, HE4, soluble mesothelin-related marker (SMR), mesothelin, and myeloperoxidase (MPO), were measured in sera of 109 patients with stages I-II ovarian cancer, 200 healthy women, and 111 patients with benign pelvic tumors. IL-6, CA 125, CK 19, IGFBPI, MIF, HE4, IL-2R, and MIP-1b, CA19-9, CA 125, CK19, CA 72-4, TSH, GH, ACTH, and prolactin were significantly higher in cancer, while Eotaxin, ErbB2, EGFR, MMP-2, MMP-3, sICAM, V-CAM, mesothelin, sE-selectin, and FSH were significantly lower in cancer as compared to healthy controls. Additionally, serum levels of CA19-9, CA 125, Cyfra 21-1, CA 72-4, prolactin, and tPAI were significantly higher and TNF-α levels were significantly lower in ovarian cancer group compared to benign group. Three different statistical methods were used to create diagnostic models: logistic regression, mixture discriminant analysis and 2D correlation. 2D correlation demonstrated the best performance offering a sensitivity of 100% at a specificity of 98.6% in a postmenopausal group. The multimarker panel offering the highest diagnostic power was comprised of 8 biomarkers: CA 125, CA 19-9, EGFR, G-CSF, Eotaxin, IL-2R, cVCAM, and MIF. In comparison with published evidence, the presented assay offers so far the best diagnostic power for early detection of ovarian cancer. The discrimination between ovarian cancer and benign pelvic disease was performed using the 2D correlation algorithm and, when utilized the multimarker panel resulted in 98.2% sensitivity at 98.7% specificity. To the best of our knowledge, thus far, this assay provides the highest diagnostic power for early detection of ovarian cancer compared to other published assays.
Artificial intelligence for thoracic radiology: from research tool to clinical practice
Authors: Lucio Calandriello, Simon L.F. Walsh
Journal: European Respiratory Journal (2021)

Artificial intelligence (AI) presents an attractive opportunity for providing decision support to radiologists, who are often overburdened by the ever-increasing number of radiographs that are requested each year [1]. Interpretation errors, reporting delays and backlogs, particularly of chest radiographs (CXR), continue to be a major problem faced by busy radiology departments. Deep learning software can provide decision support to radiologists. New evidence shows that these tools are almost ready for implementation in clinical practice. <https://bit.ly/3vk4h5t>
Abstract 16111: Clinical Application of Deep Learning for Stress Analysis of Ascending Thoracic Aortic Aneurysms
Authors: Imon Rahaman, Zhongjie Wang, Yue XUAN, Liang Ge, Elaine E Tseng
Journal: Circulation (2020)

Introduction: Current guidelines for elective surgery of ascending thoracic aortic aneurysms (aTAAs) use aneurysm size as primary determinant for risk stratification of adverse events. Biomechanically, dissection may occur when wall stress exceeds wall strength. A widespread method for stress analysis is structural finite-element analysis (FEA). Patient-specific aortic geometries are easily obtainable and stress distributions can potentially predict risk of dissection. However, FEA is a time-consuming and difficult procedure. To bypass this issue, a recent study has developed the first deep learning (DL) approach for a fast and accurate estimation of aortic wall stress distributions. Hypothesis: In this study, we assessed the hypothesis that this deep learning approach can be applied to a large clinical dataset. Model performance was measured by comparing FEA and DL stress predictions in parallel. Methods: Patients with aTAA (n = 169) were studied. Patient-specific aneurysm geometries were obtained from ECG-gated computed tomography. Shapes were represented by hexahedral meshes with 9648 nodes and 6336 solid elements. FEA peak wall stresses and stress distributions were determined using LS-DYNA software with user-defined fiber-embedded material models under systolic pressure. The DL model was implemented in Julia and consisted of unsupervised and supervised learning algorithms. Training was performed on a training set of 152 shapes and testing set of 17 shapes with 10-fold cross-validation. Mean absolute error (MAE) and absolute error of peak stress values (APE) were used to compare DL model predictions with FEA values considered to be ground truth. Results: Average stress values predicted by our DL model were 175.64 ± 4.17 kPa and 95.69 ± 2.15 kPa in the circumferential and longitudinal direction, respectively. We computed a MAE of 5.06 ± 1.08 kPa and APE of 2.58 ± 1.39 kPa in the circumferential direction and MAE of 4.51 ± 0.98 kPa and APE of 2.32 ± 1.84 kPa in the longitudinal direction. Conclusions: DL model trained exclusively on clinical data was able to accurately predict stress distributions on complex aortic geometries. Fast and accurate stress predictions will facilitate real-time clinical applications for the risk assessment of aTAAs.
Abstract 14739: Temporal Trends, Predictors and Outcomes of Acute Ischemic Stroke in Acute Myocardial Infarction in the United States
Authors: Sri Harsha Patlolla, Gaurav Aggarwal, Saurabh Aggarwal, Saraschandra Vallabhajosyula
Journal: Circulation (2020)

Introduction: There are limited contemporary data on prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods: Adult (&gt;18 years) AMI admissions using the National Inpatient Sample database (2000-2017) were evaluated for in-hospital AIS. Outcomes of interest included in-hospital mortality, hospitalization costs, length of stay, and use of tracheostomy and percutaneous endoscopic gastrostomy (PEG). The discharge destination was used to classify AIS survivors into good and poor functional outcomes with poor (moderate to severe disability) defined as discharge to extended care facility including short-term hospital/rehabilitation facility, intermediate care or long-term care facilities. Results: Of a total 11,622,528 AMI admissions, 183,896 (1.6%) had concomitant AIS. Over the 18-year period, AIS rates were stable in STEMI admissions and decreased in NSTEMI (p&lt;0.001). Compared to those without, the AIS cohort was on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias. The AMI-AIS admissions received less frequent coronary angiography (46.9% vs. 63.8%) and percutaneous coronary angiography (22.7% vs 41.8%) (p&lt;0.001). Female sex, non-White race, higher comorbidity, ST-segment-elevation AMI presentation, atrial fibrillation/flutter, use of mechanical circulatory support and invasive mechanical ventilation were identified as individual predictors of AIS after AMI. The AIS cohort had higher in-hospital mortality (16.4% vs. 6.0%; adjusted OR 1.75 [95% CI 1.72-1.78]; p&lt;0.001) with a steady decrease in the adjusted in-hospital mortality in over the 18-year period (21% in 2000 vs 17% in 2017). The AIS cohort had longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and PEG, and less frequent discharges to home (all p&lt;0.001). In AMI-AIS survivors (N=153,318), 57.3% had a poor functional outcome with temporal trends showing a slight increase in recent years (57% in 2000 vs 62% in 2017). Conclusions: AIS is associated with significantly higher in-hospital mortality and poor functional outcomes in AMI admissions. Despite improvement in in-hospital mortality, poor functional outcomes remain high.
Abstract 12932: The ABO Blood Group of Donor Hearts Determine the Impact of Cold Preservation Duration on Heart Transplant Outcomes
Authors: Paul C TANG, Jonathan W Haft, IENGLAM LEI, Zhong Wang, Eugene Chen, Ashraf Abou el ela, Bertram Pitt, Keith D Aaronson, Francis D Pagani
Journal: Circulation (2020)

Background: Tolerance of donor hearts of different ABO blood types to allograft ischemic time has not been previously examined. Objectives: We determined the impact of allograft ischemic time on heart transplant outcomes with differing ABO donor organ types. Methods: We identified 32,454 heart transplants (2000-2016) from the United Network for Organ Sharing database. Continuous variables were analyzed with t-test and categorical variables were compared with Chi-squared test. Survival was determined using log-rank or Cox regression tests. Propensity matching adjusted for preoperative variables. Results: Comparing allograft ischemic times &lt;4 hours (hr, n=6579) versus ≥4hr (n=25,875), the odds ratio (OR) for death at 15 years following prolonged allograft ischemic time (≥4hrs) for blood type O, A, B, and AB were 1.106 (P&lt;0.001), 1.062 (P&lt;0.001), 1.059 (P=0.062), 1.114 (P=0.221), respectively. Unadjusted data demonstrated higher mortality for transplantation of O versus non-O donor hearts for allograft ischemic times ≥4 hours (OR=1.164, P&lt;0.001). Following propensity matching, O donor hearts continued to have worse survival if preserved for ≥4hrs (OR=1.137, P=0.008), but not if allograft ischemic time was &lt;4hrs (OR=1.042, P=0.113). In a matched group with ≥4hrs of allograft ischemic time, patients receiving O donor organs were more likely to experience death from primary allograft dysfunction (2.5% vs 1.7%, P=0.052) and chronic allograft rejection (1.9% versus 1.1%, P=0.021). No difference in death from primary allograft graft dysfunction or chronic allograft rejection was seen with &lt;4hr of allograft ischemic time (P&gt;0.150). Conclusions: Compared with non-O hearts, transplantation with O donor hearts stored for ≥4hrs leads to worse survival, with higher rates of primary graft dysfunction and chronic rejection. Caution should be practiced when considering donor hearts with the O blood type when extended cold preservation times are anticipated.
Abstract 13084: Epsilon Waves on Electrocardiograms in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy: Relationship to Left Ventricular Invasion or Heart Compression Due to an Enlarged Right Ventricle
Authors: Nobusada FUNABASHI, Yoshio Kobayashi
Journal: Circulation (2020)

Introduction: Epsilon waves on V1-3 leads are known as one of the specific lead ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) that suggests the presence of RV conduction delay. Four dimensional (4D) cardiac CT visualizes ARVC characteristics, such as fat and fibrotic invasion in RV (RVM) and left ventricular (LV) myocardium (LVM), an enlarged RV, reduced RV motion, and bulging. Hypothesis: If epsilon waves are observed in V4-6 leads, this finding suggests the occurrence of LV invasion in ARVC. Another hypothesis exists in which extreme RV enlargement may compress the LV and cause clockwise rotation; an enlarged RV itself may cause epsilon waves in V4-6 leads. Methods: This is a retrospective analysis of 17 patients (11 males, 57 ± 17 years) with suspected ARVC who underwent cardiac CT. On 4D CT, nine met 2010 ARVC task force criteria. Results: All nine patients had epsilon waves on ECG. Five had fat and fibrotic invasion in the LVM but four did not. We divided nine into the following five groups by CT findings. On CT, a markedly enlarged RV compressed the LV to the left side and a fibro fatty change were observed exclusively in RVM (gp 1, N=1) or were observed in both RVM and LVM (gp 2, N=2). A moderately enlarged RV without compression of the LV to the left side and a fibro fatty change were observed exclusively in RVM (gp 3, N=3), or observed in both RVM and LVM (gp 4, N=2). The complications of severe mitral valve regurgitation, a markedly enlarged LV, and a fibro fatty change were observed in both RVM and LVM (gp 5, N=1). A patient in gp 1 showed epsilon waves in V1-6 leads. Patients in gp 2 showed epsilon waves in V1-6 (N=1), and V3-5 (N=1) leads, respectively. Patients in gp 3 showed epsilon waves in V1-4 (N=2), and V1-3 (N=1) leads, respectively. Patients in gp 4 showed epsilon waves in V1-3 (N=1), and V1, 2 (N=1) leads, respectively. A patient in gp 5 showed epsilon waves in V4-6 leads. Conclusions: The distribution of epsilon waves on ECG in patients with confirmed ARVC by cardiac CT was highly influenced by the degree of LV compression due to a markedly enlarged RV on CT rather than the presence of LV invasion. Also, structural change due to complicated heart diseases, such as valvular diseases, may also influence the distribution of epsilon waves in ARVC.
Long-term outcomes and predictive ability of non-invasive scoring systems in patients with non-alcoholic fatty liver disease
Authors: Ramy Younes, Gian Paolo Caviglia, Olivier Govaere, Chiara Rosso, Angelo Armandi, Tiziana Sanavia, Grazia Pennisi, Antonio Liguori, Paolo Francione, Rocío Gallego-Durán, Javier Ampuero, Maria J. Garcia Blanco, Rocio Aller, Dina Tiniakos, Alastair Burt, Ezio David, Fabio M. Vecchio, Marco Maggioni, Daniela Cabibi, María Jesús Pareja, Marco Y.W. Zaki, Antonio Grieco, Anna L. Fracanzani, Luca Valenti, Luca Miele, Piero Fariselli, Salvatore Petta, Manuel Romero-Gomez, Quentin M. Anstee, Elisabetta Bugianesi
Journal: Journal of Hepatology (2021)