tbuckley/cabot-search huggingface dataset:
FRI0169 First validation of consensus definitions for mri lesions in the sacroiliac joint by the assessments in spondyloarthritis international society (ASAS) mri group
Authors: W.P. Maksymowych, U. Weber, S.J. Pedersen, X. Baraliakos, P. Machado, J. Sieper, D. Poddubnyy, S. Wichuk, R.G. Lambert, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The diversity of MRI lesions in the sacroiliac joints of patients with axial spondyloarthritis (axSpA) has only recently been appreciated and consistent terminology, descriptions, and definitions have not yet been internationally accepted. The ASAS MRI group has generated updated consensus lesion definitions (ASAS_MRI_def<sup>n</sup>) and these now require validation in multi-reader exercises to support widespread adoption for clinical practice and research. <h3>Objectives</h3> To assess the reliability of detection of active and structural lesions as defined by (ASAS_MRI_def<sup>n</sup>) on MRI images from the ASAS Classification Cohort (ASAS-CC) in a multireader ASAS exercise. <h3>Methods</h3> ASAS_MRI_def<sup>n</sup> were recorded in an eCRF that comprises global assessment (lesion present/absent) and detailed scoring (SPARCC SIJ inflammation, SPARCC SIJ structural). MRI images were available in a variety of formats (DICOM (n=175), JPEG(n=71), DICOM film(n=32)) and sequences, axial and semicoronal orientations, from 278 of the 495 cases who had MRI performed in the ASAS-CC. Image quality was considered sufficient to record global data by 6 central readers in all cases. An additional reader assessed only images in DICOM format (n=175). Detailed SPARCC scoring data was based only on assessment of images in DICOM format. Detection of lesions assessed as present/absent by global assessment was analysed using kappa. Reliability of detailed scoring was analysed by intraclass correlation coefficient (ICC). <h3>Results</h3> Reliability of detection of active and structural lesions was comparable and somewhat better when DICOM images were evaluated (table 1). The most frequently detected active lesion, subchondral inflammation, was detected to a comparable degree of reliability as the most frequently detected structural lesion, erosion. Fat metaplasia in the joint space (backfill) and ankylosis were also reliably detected despite low frequency of occurrence in this cohort. Mean ICC for detailed scores were BME-0.84, Erosion-0.55, Fatty lesion (any)−0.61, Fatty lesion (&gt;1 cm depth)−0.55, Sclerosis-0.73, Fat metaplasia in joint space-0.36, Ankylosis-0.97, Bone bud-0.07. <h3>Conclusions</h3> The reliability of the ASAS_MRI_def<sup>n</sup> was substantial for the most frequently detected lesions. <h3>Disclosure of Interest</h3> None declared
Abstract 3588: ACTallo: A novel approach using gamma-delta T cells to allogeneic cellular therapy to treat cancer
Authors: Mo Dao, Melinda Mata, Leonie Alten, Aleksandra Nowicka, Sabrina Kuttruff, Sarah Missel, Ali Mohamed, Toni Weinschenk, Yannick Bulliard, Steffen Walter
Journal: Cancer Research (2018)

Abstract Adoptive cellular therapy (ACT) has dramatically changed the landscape of cancer immunotherapy; however, the complex manufacture of individualized products from late-stage, heavily pre-treated cancer patients, together with high cost-of-goods, encourages the development of simpler ‘off-the-shelf' alternatives. The unique properties of γδ (gamma-delta) T cells make them a seductive candidate for effective allogeneic ACT. In contrast to αβ T cells, γδ T cells are endowed with intrinsic antitumor activity while unable to induce graft-versus-host disease. γδ T cells have a high proliferative potential before exhibiting exhaustion. Moreover, in the context of αβ TCR-engineered ACT, γδ T cells pose a lesser risk of off-target toxicity, due to the absence of expression of endogenous αβ TCR and hence, risk of mispairing with the engineered αβ TCR. Here, we will present the ACTallo® platform, which combines the unique properties of γδ T cells with Immatics' XPRESIDENT® target/TCR discovery platform. The ACTallo® process selectively expands Vγ9Vδ2 T cells that are retrovirally-transduced to co-express CD8 together with a tumor-specific αβ TCR. Over a period of 45 days or less, ACTallo® γδ T cells can expand &amp;gt;30,000 fold. γδ T cells obtained this way recognize tumor cells, express cytokines, degranulate and kill tumor cells specifically. In addition, ACTallo® γδ T cells show no signs of exhaustion after expansion, as evidenced by the lack of expression of PD1, TIM3 or LAG3. ACTallo® is intended to overcome the limitation of autologous cellular therapies towards off-the-shelf approach, by combining the large-scale expansion potential of allogeneic γδ T cells with novel TCRs against XPRESIDENT® mass-spectrometry guided tumor-specific targets. Citation Format: Mo Dao, Melinda Mata, Leonie Alten, Aleksandra Nowicka, Sabrina Kuttruff, Sarah Missel, Ali Mohamed, Toni Weinschenk, Yannick Bulliard, Steffen Walter. ACTallo: A novel approach using gamma-delta T cells to allogeneic cellular therapy to treat cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3588.
2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
Authors: Karen K. Stout, Curt J. Daniels, Jamil A. Aboulhosn, Biykem Bozkurt, Craig S. Broberg, Jack M. Colman, Stephen R. Crumb, Joseph A. Dearani, Stephanie Fuller, Michelle Gurvitz, Paul Khairy, Michael J. Landzberg, Arwa Saidi, Anne Marie Valente, George F. Van Hare
Journal: Circulation (2018)

PREAMBLESince 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health.These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a cornerstone for quality cardiovascular care.The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each organization volunteer their time to the writing and review efforts.Guidelines are official policy of the ACC and AHA. Intended UsePractice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular disease.The focus is on medical practice in the United States, but guidelines developed in collaboration with other organizations can have a global impact.Although guidelines may be used to inform regulatory or payer decisions, they are intended to improve patients' quality of care and align with patients' interests.Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances and should not replace clinical judgment. Clinical ImplementationManagement in accordance with guideline recommendations is effective only when followed by both practitioners and patients.Adherence to recommendations can be enhanced by shared decision-making between clinicians and patients, with patient engagement in selecting interventions on the basis of individual values, preferences, and associated conditions and comorbidities.
Determinants of Cerebral Oxygenation During Cardiac Surgery
Authors: GeorgNollert, PatrickMöhnle, PeterTassani-Prell, BrunoReichart
Journal: Circulation (1995)

Background Neuropsychological deficits after cardiac surgery are attributed to the side effects of cardiopulmonary bypass (CPB). To protect the brain from ischemic damage, the influences of temperature, blood pressure, blood gases, acid-base status, and hemodilution on cerebral oxygenation have to be elucidated and quantified. Methods Forty-one consecutive patients were investigated during cardiac surgery while on CPB. Operative management included moderate hypothermia of 26°C and the alpha-stat pH management. With near-infrared spectrophotometry, changes in oxygenated hemoglobin (Hbo2, representing oxygen delivery) and oxidized cytochrome a,a3 (Cto2, cellular oxygenation) in brain tissue were obtained noninvasively. In addition, venous saturation of the brain was measured via a catheter in the jugular bulb (SBJo2). The influence of operative management parameters on cerebral oxygenation was calculated by univariate and multiple regression analyses. Results Before and after CPB there was no significant mu...
Clinical Course and Management of Hypertrophic Cardiomyopathy
Authors: Barry J. Maron
Journal: New England Journal of Medicine (2018)

HCM is the most common genetic disorder of the heart, with 1 case per 200 to 500 persons, and often remains clinically silent. HCM is the most common cause of sudden death in athletes, but pharmacologic, electrical, and surgical interventions have reduced mortality to 0.5% per year.
Robot-assisted Partial Adrenalectomy for the Treatment of Conn's Syndrome: Surgical Technique, and Perioperative and Functional Outcomes
Authors: Giuseppe Simone, Umberto Anceschi, Gabriele Tuderti, Leonardo Misuraca, Antonio Celia, Bernardino De Concilio, Manuela Costantini, Antonio Stigliano, Francesco Minisola, Mariaconsiglia Ferriero, Salvatore Guaglianone, Michele Gallucci
Journal: European Urology (2018)
BAG3 and Hsc70 Interact With Actin Capping Protein CapZ to Maintain Myofibrillar Integrity Under Mechanical Stress
Authors: AkinoriHishiya, ToshioKitazawa, ShinichiTakayama
Journal: Circulation Research (2010)

Rationale:A homozygous disruption or genetic mutation of the bag3 gene, a member of the Bcl-2–associated athanogene (BAG) family proteins, causes cardiomyopathy and myofibrillar myopathy that is characterized by myofibril and Z-disc disruption. However, the detailed disease mechanism is not yet fully understood. Objective:bag3−/− mice exhibit differences in the extent of muscle degeneration between muscle groups with muscles experiencing the most usage degenerating at an accelerated rate. Usage-dependent muscle degeneration suggests a role for BAG3 in supporting cytoskeletal connections between the Z-disc and myofibrils under mechanical stress. The mechanism by which myofibrillar structure is maintained under mechanical stress remains unclear. The purpose of the study is to clarify the detailed molecular mechanism of BAG3-mediated muscle maintenance under mechanical stress. Methods and Results:To address the question of whether bag3 gene knockdown induces myofibrillar disorganization caused by mechanical ...
Abstract 3751: Inhibition of A2AR by AZD4635 induces anti-tumor immunity alone and in combination with anti-PD-L1 in preclinical models
Authors: Alexandra Borodovsky, Yanjun Wang, Minwei Ye, Joseph C. Shaw, Kris Sachsenmeier, Nanhua Deng, Kelly Goodwin, James D. Clarke, Richard Goodwin, Nicole Strittmatter, Carl Hay, Vasu Sah, Lawson Deborah, Corinne Reimer, Miles Congreve, Jonathan Mason, Fiona Marshall, Paul Lyne, Richard Woessner
Journal: Cancer Research (2018)

Abstract Adenosine signaling through the high affinity adenosine 2A receptor (A2AR) on immune cells elicits a range of immunosuppressive effects which can promote tumor growth and limit the efficacy of immune checkpoint inhibitors. AZD4635 (HTL-1071) is a potent and selective oral A2AR antagonist, currently in a Phase 1 clinical trial as a single agent and in combination with durvalumab (anti-PD-L1 Ab) in patients with solid malignancies. In functional in vitro assays, the IC50 of AZD4635 for inhibition of A2AR signaling is dependent on adenosine concentrations and ranges from 1, 10.0, 143 nM in the presence of 0.1, 1, 10 μM adenosine, respectively. However, full understanding of the impact of adenosine on AZD4635 mediated anti-tumor responses requires characterization of intratumoral adenosine concentration and spatial heterogeneity. Using a novel LC/MS based method, measurement of intratumoral adenosine concentrations in a panel of syngeneic tumor models demonstrated a wide range of adenosine levels (5-122 μM). Additionally, measurement of intratumoral adenosine by desorption electrospray ionisation - mass spectroscopy (DESI-MS) demonstrated that adenosine levels are spatially heterogeneous, with levels varying up to 50-fold among regions of a single tumor. High intratumoral adenosine concentrations were correlated with decreased intratumoral CD8 infiltration in vivo. The therapeutic benefit of A2AR blockade alone and in combination with anti-PD-L1 was evaluated in a panel of syngeneic mouse tumor models with varying adenosine concentrations. In sensitive models, inhibition of A2AR signaling with AZD4635 led to a dose dependent reduction in tumor growth alone and in combination with checkpoint inhibitors. Tumors harvested from the treated mice exhibited increases in the functional activity of T cell and myeloid subsets. These results demonstrate that AZD4635 is a potent and selective A2AR inhibitor, that blockade of A2AR signaling with an inhibitor such as AZD4635 can reduce tumor burden and enhance antitumor immunity. Citation Format: Alexandra Borodovsky, Yanjun Wang, Minwei Ye, Joseph C. Shaw, Kris Sachsenmeier, Nanhua Deng, Kelly Goodwin, James D. Clarke, Richard Goodwin, Nicole Strittmatter, Carl Hay, Vasu Sah, Lawson Deborah, Corinne Reimer, Miles Congreve, Jonathan Mason, Fiona Marshall, Paul Lyne, Richard Woessner. Inhibition of A2AR by AZD4635 induces anti-tumor immunity alone and in combination with anti-PD-L1 in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3751.
Abstract 15949: High Intensity Interval Training is Superior to Continuous Training and Reverses RV Remodeling and Dysfunction in a Rat Model of Pulmonary Hypertension
Authors: Mary Beth Brown, Evandro Neves, Rachel Novack, Amanda Fisher, Robert Presson, Irina Petrache, Jeffrey Kline, Tim Lahm
Journal: Circulation (2015)

Exercise appears to have overall benefit in pulmonary arterial hypertension (PAH); however, studies to date indicate little effect on the elevated pulmonary pressure or RV hypertrophy (RVH) and dysfunction associated with the disease. High intensity interval training (HIIT) is reported to be superior to the more customary prolonged continuous exercise training (CExT) protocol for chronic heart failure but has not been tested for PAH. Therefore, we investigated impact of a 6 wk HIIT vs. CExT treadmill program in a monocrotaline rat model of mild PAH (MCT, 40 mg/kg) on indicators of disease progression. Methods: Treadmill training was performed 5x/wk in male Sprague-Dawley MCT rats (250-300g), following a protocol of either HIIT (5 cycles of 2 min at ~90% VO 2 reserve [VO 2 R] + 3 min at 30% VO 2 R; n=8), or low intensity CExT (60 min at 50% VO 2 R; n=7). Statistical analysis was performed by one-way ANOVA. Results: MCT-induced decrements in VO 2 max were ameliorated by both HIIT and CExT (p &lt; 0.01 vs. sedentary MCT rats, MCT-SED, n=6), and were similar to healthy controls (CON, n=6). Most importantly, RV systolic pressure (RVSP, in mmHg; via Millar catheter) and RVH (ratio of RV to LV+S mass) were lowered (p&lt;0.05) only by HIIT (28.7±2, and 0.32±0.02) and not by CExT (44.1±3, and 0.43±0.01) vs. MCT-SED (40.2±3.2, and 0.41±0.02). Cardiac output (Δ from baseline in μl, via RV echocardiography) was also improved by HIIT (117±28) vs. MCT-SED (6±42, p=0.04). Additional hemodynamic recordings during running, via novel implantable telemetry (DSI), were obtained serially at pre- and 2, 4, 6, and 8 wks post-MCT, and revealed ‘surges’ in RVSP during HIIT, vs. a steady RVSP pattern during CExT. Pulmonary eNOS (per immunoblotting) was increased (p&lt;0.05) with HIIT, consistent with greater endothelial stimulation. Conclusions: HIIT is superior to CExT for improving hemodynamics and RV remodeling and dysfunction in MCT rats and warrants further investigation in other models and in patients. More favorable outcomes may be explained by greater sheer-stress mediated vascular endothelial adaptation to HIIT stimulus, or lower cumulative training-induced RV wall stress with the briefer HIIT session duration.
Abstract 3310: Non-invasive diagnosis of colorectal cancer via targeted high-throughput DNA methylation sequencing of circulating tumor DNA (ctDNA)
Authors: Xianrui Wu, Jiacheng Chuan, Tuo Hu, Tingting Peng, Meng Yang, Hui Shen, Peter Laird, Yangbin Gao, Xuyu Cai, Weihong Xu, Jian-bing Fan, Ping Lan
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) commonly develops from precancerous polyps. Most polyps are benign. The current screening method involves stool tests and colonoscopy, which is an unpleasant procedure. Even though stool DNA-based approach has been developed, it is still a clinical challenge to differentiate benign complications and malignant CRC. We took the approach of high-throughput DNA bisulfide sequencing of tissue samples to identify cancer-specific methylation signatures. We learned methylation patterns by in-depth data mining and then applied pattern recognition approach to classify plasma samples. From a cohort of 70 pairs of tumor-normal matched tissue samples, we identified 1062 differential methylation markers. Next, we applied a greedy optimization algorithm to build a malignancy classification model using a training set of 118 plasma samples (malignant CRC: 56, benign complications: 23, healthy subjects: 39). In the training set, we achieved an AUC of 91.9% (95%CI: 87.3-96.5%). In an independent test set of 150 plasma samples (malignant CRC: 56, benign complications: 23, healthy subjects: 71), we achieved an AUC of 92.9% (95%CI: 88.3%~97.5%). Specifically, the model had a sensitivity of 91.1% for the identification of malignant CRC, and a specificity of 84.5% and 78.3% for healthy subjects and benign complications respectively. Our assay was demonstrated to be very sensitive towards early-stage CRC detection, with a sensitivity of 76.5% and 95% for stage I and II CRC respectively. The performance of this assay still awaits further validation in a large-scale clinical trial. In summary, we have developed a highly sensitive blood-based non-invasive diagnostic assay for the identification of malignant CRC, which can aid clinical decisions for doctors. This approach can also be extended to non-invasive early screening for various other cancer types. Citation Format: Xianrui Wu, Jiacheng Chuan, Tuo Hu, Tingting Peng, Meng Yang, Hui Shen, Peter Laird, Yangbin Gao, Xuyu Cai, Weihong Xu, Jian-bing Fan, Ping Lan. Non-invasive diagnosis of colorectal cancer via targeted high-throughput DNA methylation sequencing of circulating tumor DNA (ctDNA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3310.
Abstract 2192: Single-molecule single-cell DNA sequencing identifies ongoing copy number evolution in BRCA breast cancers
Authors: Haowei Du, Alexander Davis, Ruli Gao, Medina Colic, Emi Sei, Min Hu, Angelica Gutierrez Barrera, Anna Casasent, Constance Albarracin, Banu Arun, Nicholas E. Navin
Journal: Cancer Research (2018)

Abstract BRCA2 germline mutation carriers have a lifetime risk of 72% for developing invasive breast cancer. Although BRCA2 has been implicated in double-stranded break repair, the role of this mutation in genome evolution and maintaining genome instability during the expansion of the primary tumor mass is not well understood. To investigate these questions, we developed a novel method for single-cell, single-molecule (SCSM) sequencing. SCSM uses a Tn5 transposase to directly fragment and ligate adapters for PCR amplification, thereby omitting the whole-genome-amplification (WGA) step, which introduces technical noise into single-cell sequencing datasets. This approach provides single-molecule data by positional barcoding, reducing WGA artifacts that are typically associated with amplification bias. We further utilize a dual-barcoding approach and acoustic liquid transfer technology to increase throughput (N=384) and reduce cost to $1 per cell using nanoliter volumes. We applied SMSC to sequence copy number profiles from ~1000 single cells from two patients with BRCA2-positive breast tumors. In both cases we identified several major clonal subpopulations that shared a set of truncal CNAs, suggesting that they evolved from a single normal epithelial cell in the breast, not multiple initiating cells. We also identified many small subclonal CNAs that further diversified the major clones, which suggests that copy number evolution was ongoing during the expansion of the primary tumor mass. These data demonstrate the technical feasibility of SMSC sequencing, and further show that minor copy number evolution is ongoing in BRCA-positive breast cancer patients. Citation Format: Haowei Du, Alexander Davis, Ruli Gao, Medina Colic, Emi Sei, Min Hu, Angelica Gutierrez Barrera, Anna Casasent, Constance Albarracin, Banu Arun, Nicholas E. Navin. Single-molecule single-cell DNA sequencing identifies ongoing copy number evolution in BRCA breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2192.
Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress
Authors: GregorTheilmeier, PeterVerhamme, StevenDymarkowski, HeikeBeck, HildeBernar, MarleenLox, StefanJanssens, Marie-ChristineHerregods, ErikVerbeken, DésiréCollen, KarlPlate, WillemFlameng, PaulHolvoet
Journal: Circulation (2002)

Background— Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques that do not cause stenosis. Methods and Results— Twenty-eight minipigs on cholesterol diet for 34 weeks and 16 control pigs were studied. Seven hypercholesterolemic pigs were withdrawn from the diet for 26 weeks. LV function was assessed with cine-MRI, myocardial blood flow with colored microspheres, and capillary density with immunohistochemistry, and microvascular endothelial cell apoptosis with terminal dUTP nick-end labeling staining. Hypercholesterolemia (17±8 versus 268±150 versus 12±10 mg/dL LDL cholesterol, control versus hypercholesterolemic versus ...
Visual Phenomena in Occipital Lobe Epilepsy
Authors: Alexander Doud, Anthony Julius, Christopher B. Ransom
Journal: JAMA Neurology (2018)

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