tbuckley/cabot-search huggingface dataset:
Liver Transplantation Outcomes in a U.S. Multicenter Cohort of 789 Patients With Hepatocellular Carcinoma Presenting Beyond Milan Criteria
Authors: Ani Kardashian, Sander S. Florman, Brandy Haydel, Richard M. Ruiz, Goran B. Klintmalm, David D. Lee, C. Burcin Taner, Federico Aucejo, Amit D. Tevar, Abhinav Humar, Elizabeth C. Verna, Karim J. Halazun, William C. Chapman, Neeta Vachharajani, Maarouf Hoteit, Matthew H. Levine, Mindie H. Nguyen, Marc L. Melcher, Alan N. Langnas, Carol A. Carney, Constance Mobley, Mark Ghobrial, Beth Amundsen, James F. Markmann, Debra L. Sudan, Christopher M. Jones, Jennifer Berumen, Alan W. Hemming, Johnny C. Hong, Joohyun Kim, Michael A. Zimmerman, Trevor L. Nydam, Abbas Rana, Michael L. Kueht, Thomas M. Fishbein, Daniela Markovic, Ronald W. Busuttil, Vatche G. Agopian
Journal: Hepatology (2020)

Background and Aims The Organ Procurement and Transplantation Network recently approved liver transplant (LT) prioritization for patients with hepatocellular carcinoma (HCC) beyond Milan Criteria (MC) who are down‐staged (DS) with locoregional therapy (LRT). We evaluated post‐LT outcomes, predictors of down‐staging, and the impact of LRT in patients with beyond‐MC HCC from the U.S. Multicenter HCC Transplant Consortium (20 centers, 2002‐2013). Approach and Results Clinicopathologic characteristics, overall survival (OS), recurrence‐free survival (RFS), and HCC recurrence (HCC‐R) were compared between patients within MC (n = 3,570) and beyond MC (n = 789) who were down‐staged (DS, n = 465), treated with LRT and not down‐staged (LRT‐NoDS, n = 242), or untreated (NoLRT‐NoDS, n = 82). Five‐year post‐LT OS and RFS was higher in MC (71.3% and 68.2%) compared with DS (64.3% and 59.5%) and was lowest in NoDS (n = 324; 60.2% and 53.8%; overall P &lt; 0.001). DS patients had superior RFS (60% vs. 54%, P = 0.043) and lower 5‐year HCC‐R (18% vs. 32%, P &lt; 0.001) compared with NoDS, with further stratification by maximum radiologic tumor diameter (5‐year HCC‐R of 15.5% in DS/&lt;5 cm and 39.1% in NoDS/&gt;5 cm, P &lt; 0.001). Multivariate predictors of down‐staging included alpha‐fetoprotein response to LRT, pathologic tumor number and size, and wait time &gt;12 months. LRT‐NoDS had greater HCC‐R compared with NoLRT‐NoDS (34.1% vs. 26.1%, P &lt; 0.001), even after controlling for clinicopathologic variables (hazard ratio [HR] = 2.33, P &lt; 0.001) and inverse probability of treatment‐weighted propensity matching (HR = 1.82, P &lt; 0.001). Conclusions In LT recipients with HCC presenting beyond MC, successful down‐staging is predicted by wait time, alpha‐fetoprotein response to LRT, and tumor burden and results in excellent post‐LT outcomes, justifying expansion of LT criteria. In LRT‐NoDS patients, higher HCC‐R compared with NoLRT‐NoDS cannot be explained by clinicopathologic differences, suggesting a potentially aggravating role of LRT in patients with poor tumor biology that warrants further investigation.
Publisher Correction: Co-opted transposons help perpetuate conserved higher-order chromosomal structures
Authors: Mayank N. K. Choudhary, Ryan Z. Friedman, Julia T. Wang, Hyo Sik Jang, Xiaoyu Zhuo, Ting Wang
Journal: Genome biology (2020)

Following publication of the original paper [1], an error was reported in the processing of Fig. 2. The correct Fig. 2 is supplied below and the original article [1] has been corrected. The publishers apologize for the error.
Radio-metal cross-linking of alginate hydrogels for non-invasive in vivo imaging
Authors: P. Stephen Patrick, Joseph C. Bear, Heather E. Fitzke, May Zaw-Thin, Ivan P. Parkin, Mark F. Lythgoe, Tammy L. Kalber, Daniel J. Stuckey
Journal: Biomaterials (2020)

Alginate hydrogels are cross-linked polymers with high water content, tuneable chemical and material properties, and a range of biomedical applications including drug delivery, tissue engineering, and cell therapy. However, their similarity to soft tissue often renders them undetectable within the body using conventional bio-medical imaging techniques. This leaves much unknown about their behaviour in vivo, posing a challenge to therapy development and validation. To address this, we report a novel, fast, and simple method of incorporating the nuclear imaging radio-metal
Effects of implementing an electronic system for the collection of patient reported symptoms on clinic note transcription length
Authors: P. W. Cobb, M. Kofstad, C. Bealer
Journal: Journal of Clinical Oncology (2007)

17035 Background: Recent advances in information technology have made the goal of incorporating patient-reported symptoms possible. Initial studies have examined the validity of these systems but no systematic work has been done to examine the impact on overall practice efficiency. The PACE (Patient Assessment, Care, and Education) System captures patient-reported symptoms, quality of life, social and family history changes, and other clinical data at every office visit. The PACE System includes the Patient Care Monitor (PCM), a standardized, comprehensive assessment of a patient's condition that allows for a self-reported review of systems (ROS) via a wireless, touch screen computer tablet. The purpose of this study was to determine if implementation of the PCM had an impact on total transcription length. Methods: The study utilized a retrospective within subjects control design comparing transcription length by physicians practicing both with and without the PCM. The PACE System was implemented in October 2004 in a main outpatient oncology site in Billings, MT (PACE site). The analysis compared transcription length by physicians who practice in the Billings office where the PACE system was available, and also in four sites in Montana and Wyoming where the PACE system was not available during the same time period (January to October 2006). All available, consecutive physician notes were analyzed from eligible physicians during the analysis period. Results: Four physicians met inclusion criteria and 8,150 notes were analyzed. The average number of dictation words at PCM sites was 406.7 as compared to 485.5 at non- PCM sites (a 16% reduction). The average number of dictation lines at the PCM sites was 54.0 as compared to 58.5 at non-PCM sites (an 8% reduction). Conclusions: Increases in the use of information technology in outpatient oncology necessitate increased understanding of the validity and utility of these systems. This study of the PACE system suggests that there may be an efficiency benefit by implementing patient self-reporting systems. No significant financial relationships to disclose.
Effect of cancer patients’ oxygen breathing during uptake phase of the study on tumor F18-FDG uptake.
Authors: Xiao-Feng Li, Goetz H. Kloecker, Vivek R. Sharma, Geetika Bhatt, Aashish D. Bhatt, Ali Cahid Civelek
Journal: Journal of Clinical Oncology (2012)

e21072 Background: We previously reported that in mice, 18 F-FDG uptake is higher in hypoxic cancer cells than well-oxygenated xenografts of human cancer cells. This enhanced uptake was abrogated by carbogen (95% O2 +5% CO2) breathing. We hypothesized that in clinical applications, oxygen breathing of the patients’ during the uptake phase may blunt the 18 F-FDG uptake of the tumor and the liver. Methods: Overnight fasted patients with blood glucose level &lt; 200 mg/dl were injected with &lt; 14.0 mCi of 18 F-FDG, and PET/CT scans were performed at 60 -80 minutes later with a Siemens PET/CT scanner. Group-1 is consisted of 11 patients who were breathing room air only, without any additional oxygen during the procedure. Group-II consisted of 12 patients who were breathing oxygen during the uptake phase. Group-III consisted of 10 patients who were breathing oxygen only at the time of scanning and not during uptake phase. Tumor FDG activities of the groups were not compared since no paired data (with and without oxygen in same patient) was available. Thus, Liver FDG activity of the patients in each group were measured as surrogate to the oxygen effect on tumor, and expressed as Liver SUV max and Liver SUV average values, and they were compared to each other to determine the statistical significance. Results: Both liver SUV max and SUV average values were significantly lower in Group-II patients who were breathing oxygen during the uptake phase compared to Group–I and Group-III (P&lt; 0.05 for both). Liver SUV max and SUV average values were not significantly different between Group–I and Group–III. In one patient who had a paired scans with and without O 2 during the uptake phase showed a significant FDG activity of the tumor when he was breathing O 2 during uptake phase. Conclusions: In cancer patients, O 2 breathing during FDG uptake phase may significantly blunt 18 F-FDG uptake, thus, in cancer patients this may decrease the accuracy of the FDG PET/CT for the detection, staging of the disease and the assessment of the therapy effect. [Table: see text]
MRI background enhancement: Its relationship with breast density and breast cancer risk
Authors: A. Kwong, J. Rosenberg, M. A. Van den Bosch, B. L. Daniel, G. Lo, D. M. Ikeda
Journal: Journal of Clinical Oncology (2007)

1539 Background: Increased breast density increases breast cancer risk. MRI breast is increasingly used for imaging as unlike mammography, the sensitivity of MRI breast is not affected by breast density but rather, the amount of background enhancement. It has been suggested that increased background enhancement may be related to the amount of proliferative breast tissue present; hence this may also be related to increased breast cancer risk. To date there have been no study published assessing background enhancement and its relation to breast cancer risk. Method: A retrospective review 45 mammography films and breast MRI scans of 36 patients (9 bilateral) with normal breast imaging was performed and scored independently by 3 radiologists for breast density using BI-RADS criteria. MRI breast density was scored on the non-contrast enhanced T1-weighted series whereas background enhancement was quantified on the first contrast-enhanced T1-weighted fat-suppressed series. Background enhancement was scored as none-minimal, mild, moderate, marked. Weighted kappa was used to assess the inter-modality agreement. A partial approximation to the Gail risk score was calculated from the available risk factors (age, menarche, number of biopsies, births and relatives with breast cancer), using coefficients from a Caucasian population; the resulting values were converted to ranks and was correlated with background enhancement. Result: There was substantial within-reader agreement between mammographic and MRI density (kappa=0.68; p=0.001). There were no correlation between background enhancement and breast density. All 6 patients with background-enhancement were pre-menopausal. Although not statistically significant (p&lt;0.37), it is suggestive that 4 of the 6 (67%) had a history of breast cancer while only 6 of the 13 premenopausal non-enhancers (46%) had cancer. Moreover, the mean of the rank risk for enhancing premenopausal women was 29.5 while the non-enhancing pre-menopausal women was 16.6 (p=0.048 by one-tailed t-test). Conclusion: We found good correlation between mammographic and MRI breast density. There was no correlation between breast density and MRI background enhancement. There is a suggestion that MRI background enhancement may be associated with a higher risk of breast cancer. No significant financial relationships to disclose.
Therapeutic Targeting of<i>SDHB</i>-Mutated Pheochromocytoma/Paraganglioma with Pharmacologic Ascorbic Acid
Authors: Yang Liu, Ying Pang, Boqun Zhu, Ondrej Uher, Veronika Caisova, Thanh-Truc Huynh, David Taieb, Katerina Hadrava Vanova, Hans Kumar Ghayee, Jiri Neuzil, Mark Levine, Chunzhang Yang, Karel Pacak
Journal: Clinical Cancer Research (2020)

Pheochromocytomas and paragangliomas (PCPG) are usually benign neuroendocrine tumors. However, PCPGs with mutations in the succinate dehydrogenase B subunit (SDHB) have a poor prognosis and frequently develop metastatic lesions. SDHB-mutated PCPGs exhibit dysregulation in oxygen metabolic pathways, including pseudohypoxia and formation of reactive oxygen species, suggesting that targeting the redox balance pathway could be a potential therapeutic approach.We studied the genetic alterations of cluster I PCPGs compared with cluster II PCPGs, which usually present as benign tumors. By targeting the signature molecular pathway, we investigated the therapeutic effect of ascorbic acid on PCPGs using in vitro and in vivo models.By investigating PCPG cells with low SDHB levels, we show that pseudohypoxia resulted in elevated expression of iron transport proteins, including transferrin (TF), transferrin receptor 2 (TFR2), and the divalent metal transporter 1 (SLC11A2; DMT1), leading to iron accumulation. This iron overload contributed to elevated oxidative stress. Ascorbic acid at pharmacologic concentrations disrupted redox homeostasis, inducing DNA oxidative damage and cell apoptosis in PCPG cells with low SDHB levels. Moreover, through a preclinical animal model with PCPG allografts, we demonstrated that pharmacologic ascorbic acid suppressed SDHB-low metastatic lesions and prolonged overall survival.The data here demonstrate that targeting redox homeostasis as a cancer vulnerability with pharmacologic ascorbic acid is a promising therapeutic strategy for SDHB-mutated PCPGs.
Genome Architecture Facilitates Phenotypic Plasticity in the Honeybee (Apis mellifera)
Authors: Elizabeth J Duncan, Megan P Leask, Peter K Dearden
Journal: Molecular Biology and Evolution (2020)

Abstract Phenotypic plasticity, the ability of an organism to alter its phenotype in response to an environmental cue, facilitates rapid adaptation to changing environments. Plastic changes in morphology and behavior are underpinned by widespread gene expression changes. However, it is unknown if, or how, genomes are structured to ensure these robust responses. Here, we use repression of honeybee worker ovaries as a model of plasticity. We show that the honeybee genome is structured with respect to plasticity; genes that respond to an environmental trigger are colocated in the honeybee genome in a series of gene clusters, many of which have been assembled in the last 80 My during the evolution of the Apidae. These clusters are marked by histone modifications that prefigure the gene expression changes that occur as the ovary activates, suggesting that these genomic regions are poised to respond plastically. That the linear sequence of the honeybee genome is organized to coordinate widespread gene expression changes in response to environmental influences and that the chromatin organization in these regions is prefigured to respond to these influences is perhaps unexpected and has implications for other examples of plasticity in physiology, evolution, and human disease.
Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death
Authors: Timothy F. Simpson, James W. Salazar, Eric Vittinghoff, Joanne Probert, Alan Iwahashi, Jeffrey E. Olgin, Phillip Ursell, Amy Hart, Ellen Moffatt, Zian H. Tseng
Journal: JAMA Internal Medicine (2020)

QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown.
High-resolution computed tomography features of 17 cases of coronavirus disease 2019 in Sichuan province, China
Authors: Simin Zhang, Huaqiao Li, Songtao Huang, Wei You, Huaiqiang Sun
Journal: European Respiratory Journal (2020)

<b>Bilateral ground-glass opacities and a combination of consolidation and ground-glass opacities mainly in the subpleural lung regions is a noteworthy HRCT feature of coronavirus disease 2019, which may help in the early diagnosis of the disease</b>http://bit.ly/2IgXcel
Abstract P501: Mobile Daily Physical Activity and Fall Risk Monitor for Lifestyle Management, Disease Prevention and Risk Alert Generation
Authors: Qingxue Zhang
Journal: Circulation (2020)

Mobile health monitoring is driving many smart health innovations. In this research, we focus on the daily physical activity and fall risk monitoring, for intelligent activity tracking and fall risk detection purpose. Physical activity is of a tremendous value to cardiac and brain health, and has been widely agreed as a metric to improve human health, foster healthy lifestyle, and mine the impacts on diverse health issues. The risk of death can actually be lowered by 20 to 30% with moderate activities for one and half an hour per week (WHO). Besides, fall risk detection is also of huge importance since each year, there are 29% of older adults having around 29 million falls and causing 7 million fall injuries (CDC). The challenge we target is how to accurately recognize diverse physical activities and fall patterns from the biomechanical dynamics sensed by the phone. More specifically, the phone sensor is leveraged to provide real-time always-on streaming of biomechanical dynamics. Then, the data is learned by a deep learning framework (long short-term memory) for activity type and fall pattern recognition. To consider real-world scenarios, the users can put the phone in either left or write waist pockets. The users have performed 9 different kinds of activities such as walking, standing up, going upstairs and jumping, as well as 8 different kinds of fall patterns such as falling backward, sitting and falling, and falling forward with protection. A total of 11,770 activities performed by 30 subjects aging from 18 to 60 have been used to evaluate the framework, yielding an accuracy as high as 95.4%. This encouraging result shows the potential of the mobile monitor in real-world application scenarios.
Neurofibromin Is an Estrogen Receptor-α Transcriptional Co-repressor in Breast Cancer
Authors: Ze-Yi Zheng, Meenakshi Anurag, Jonathan T. Lei, Jin Cao, Purba Singh, Jianheng Peng, Hilda Kennedy, Nhu-Chau Nguyen, Yue Chen, Philip Lavere, Jing Li, Xin-Hui Du, Burcu Cakar, Wei Song, Beom-Jun Kim, Jiejun Shi, Sinem Seker, Doug W. Chan, Guo-Qiang Zhao, Xi Chen, Kimberly C. Banks, Richard B. Lanman, Maryam Nemati Shafaee, Xiang H.-F. Zhang, Suhas Vasaikar, Bing Zhang, Susan G. Hilsenbeck, Wei Li, Charles E. Foulds, Matthew J. Ellis, Eric C. Chang
Journal: Cancer Cell (2020)

We report that neurofibromin, a tumor suppressor and Ras-GAP (GTPase-activating protein), is also an estrogen receptor-α (ER) transcriptional co-repressor through leucine/isoleucine-rich motifs that are functionally independent of GAP activity. GAP activity, in turn, does not affect ER binding. Consequently, neurofibromin depletion causes estradiol hypersensitivity and tamoxifen agonism, explaining the poor prognosis associated with neurofibromin loss in endocrine therapy-treated ER+ breast cancer. Neurofibromin-deficient ER+ breast cancer cells initially retain sensitivity to selective ER degraders (SERDs). However, Ras activation does play a role in acquired SERD resistance, which can be reversed upon MEK inhibitor addition, and SERD/MEK inhibitor combinations induce tumor regression. Thus, neurofibromin is a dual repressor for both Ras and ER signaling, and co-targeting may treat neurofibromin-deficient ER+ breast tumors.
Abstract P6-03-15: MCL-1 confers oncogenic role in breast cancer through modulating drug resistance and cancer stemness by targeting MRP1
Authors: Yuzhu Zhang, Junyan Huang, Fengjie Bie, Liping Ren, Qianjun Chen
Journal: Cancer Research (2020)

Abstract Background: Breast cancer is the most common malignant tumor and the leading killer in women. Chemotherapy is one of the most important treatments for breast cancer. However, development of chemotherapy resistance is the main reason for 20-30% of breast cancer patients getting metastasis and leading to death. MCL-1, the anti-apoptotic protein, is not clarified in conforing chemotherapy resistance of Breast cancer. This work is mainly to prove that MCL-1 is the role of chemotherapy resistance and stemness of Breast cancer.Methods: We used large gene panels to detect pathological sections of tumors in drug-resistant and sensitive patients. We validated protein profiling by IHC in a larger cohort of samples. We performed the function of MCL-1 by knockdown and overexpression in vitro and in vivo. Luciferase assay and CHIP assay were used to prove the regulatory network between MCL-1 and MRP1.Result: Here, we find that MCL-1 is highly expressed in drug-resistant breast cancer tissues than sensitive. Functional studies reveal that MCL-1 plays important role in drug resistant by regulating apoptosis in breast cancer cells. We identity that knockdown of MCL-1 enhances sensitivity and reduces stem cell of breast cancer in vitro and in vivo, while overexpression has the opposite effect. Furthermore, by down and up regulation MCL-1, we show that MCL-1 regulates the expression of MRP1 (ABCC1) in breast cancer cells. Finally, we demonstrate that MCL-1 regulates ABCC1 expression through binding to its specific promoter region and promoting its transcription levels.Conclusion: Our work highlight the role of MCL-1 in chemoresistance and stemness, suggesting it could be used as a new clinical marker for breast cancer with drug resistance.Keyword:MCL-1, Breast cancer, chemoresistance, stemness, MRP1. Funding: Guangdong Natural Science Foundation No. 2017A030313719;Foundation Project of Guangzhou University of Traditional Chinese Medicine, No. XKP2019002. Citation Format: Yuzhu Zhang, Junyan Huang, Fengjie Bie, Liping Ren, Qianjun Chen. MCL-1 confers oncogenic role in breast cancer through modulating drug resistance and cancer stemness by targeting MRP1 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-15.
Ventricular Arrhythmias in Myocarditis
Authors: Giovanni Peretto, Simone Sala, Stefania Rizzo, Anna Palmisano, Antonio Esposito, Francesco De Cobelli, Corrado Campochiaro, Giacomo De Luca, Luca Foppoli, Lorenzo Dagna, Gaetano Thiene, Cristina Basso, Paolo Della Bella
Journal: Journal of the American College of Cardiology (2020)
Early prediction of circulatory failure in the intensive care unit using machine learning
Authors: Stephanie L. Hyland, Martin Faltys, Matthias Hüser, Xinrui Lyu, Thomas Gumbsch, Cristóbal Esteban, Christian Bock, Max Horn, Michael Moor, Bastian Rieck, Marc Zimmermann, Dean Bodenham, Karsten Borgwardt, Gunnar Rätsch, Tobias M. Merz
Journal: Nature Medicine (2020)