tbuckley/cabot-search huggingface dataset:
Clinically Relevant and Minimally Invasive Tumor Surveillance of Pediatric Diffuse Midline Gliomas Using Patient-Derived Liquid Biopsy
Authors: Eshini Panditharatna, Lindsay B. Kilburn, Mariam S. Aboian, Madhuri Kambhampati, Heather Gordish-Dressman, Suresh N. Magge, Nalin Gupta, John S. Myseros, Eugene I. Hwang, Cassie Kline, John R. Crawford, Katherine E. Warren, Soonmee Cha, Winnie S. Liang, Michael E. Berens, Roger J. Packer, Adam C. Resnick, Michael Prados, Sabine Mueller, Javad Nazarian
Journal: Clinical Cancer Research (2018)

Pediatric diffuse midline glioma (DMG) are highly malignant tumors with poor clinical outcomes. Over 70% of patients with DMG harbor the histone 3 p.K27M (H3K27M) mutation, which correlates with a poorer clinical outcome, and is also used as a criterion for enrollment in clinical trials. Because complete surgical resection of DMG is not an option, biopsy at presentation is feasible, but rebiopsy at time of progression is rare. While imaging and clinical-based disease monitoring is the standard of care, molecular-based longitudinal characterization of these tumors is almost nonexistent. To overcome these hurdles, we examined whether liquid biopsy allows measurement of disease response to precision therapy.We established a sensitive and specific methodology that detects major driver mutations associated with pediatric DMGs using droplet digital PCR (n = 48 subjects, n = 110 specimens). Quantification of circulating tumor DNA (ctDNA) for H3K27M was used for longitudinal assessment of disease response compared with centrally reviewed MRI data.H3K27M was identified in cerebrospinal fluid (CSF) and plasma in 88% of patients with DMG, with CSF being the most enriched for ctDNA. We demonstrated the feasibility of multiplexing for detection of H3K27M, and additional driver mutations in patient's tumor and matched CSF, maximizing the utility of a single source of liquid biome. A significant decrease in H3K27M plasma ctDNA agreed with MRI assessment of tumor response to radiotherapy in 83% (10/12) of patients.Our liquid biopsy approach provides a molecularly based tool for tumor characterization, and is the first to indicate clinical utility of ctDNA for longitudinal surveillance of DMGs.
Phase I pharmacological study of continuous chronomodulated capecitabine treatment
Authors: J. Roosendaal, B.A.W. Jacobs, D. Pluim, H. Rosing, B. Nuijen, J.H. Beijnen, A.D.R. Huitema, J.H.M. Schellens, S. Marchetti
Journal: Annals of Oncology (2018)
Chemoradiotherapy and Local Excision for Organ Preservation in Early Rectal Cancer—The End of the Beginning?
Authors: Julio Garcia-Aguilar
Journal: JAMA Surgery (2018)

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Essentials for a successful registry: valid data, the right questions and timely execution
Authors: I. Garcia-Doval, R.S. Stern
Journal: British Journal of Dermatology (2018)

Linked Articles: Gerbens et al. Br J Dermatol 2018; doi: 10.1111/bjd.16714. Garcia‐Doval et al. Br J Dermatol 2018; 179:863–871. Grinich et al. Br J Dermatol 2018; 179:540–541.
Immuno-oncology biomarker study in a large cohort of LC-SCRUM-Japan: LC-SCRUM-IBIS
Authors: Kei Kunimasa, Kiyotaka Yoh, Shingo Matsumoto, Naoki Furuya, Shingo Miyamoto, Satoshi Oizumi, Eriko Tabata, Shunichi Sugawara, Masahiro Kodani, Norio Okamoto, Satoshi Hara, Yuichiro Hayashi, Noriko Motoi, Genichiro Ishii, Koichi Goto
Journal: Annals of Oncology (2018)
Evaluation of hypertension and hand-foot syndrome as markers of anlotinib efficacy in advanced soft tissue sarcoma
Authors: Z. Fang, Y. Chi, Y. Yao, S. Wang, G. Huang, Q. Cai, G. Shang, G. Wang, G. Qu, Q. Wu, Y. Jiang, J. Song, J. Chen, X. Zhu, Z. Cai, C. Bai, Y. Lu, Z. Yu, J. Shen, J. Cai
Journal: Annals of Oncology (2018)
Complement C5a Fosters Squamous Carcinogenesis and Limits T Cell Response to Chemotherapy
Authors: Terry R. Medler, Dhaarini Murugan, Wesley Horton, Sushil Kumar, Tiziana Cotechini, Alexandra M. Forsyth, Patrick Leyshock, Justin J. Leitenberger, Molly Kulesz-Martin, Adam A. Margolin, Zena Werb, Lisa M. Coussens
Journal: Cancer Cell (2018)
Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis
Authors: William L. Hasler, Laura A. Wilson, Linda A. Nguyen, William J. Snape, Thomas L. Abell, Kenneth L. Koch, Richard W. McCallum, Pankaj J. Pasricha, Irene Sarosiek, Gianrico Farrugia, Madhusudan Grover, Linda A. Lee, Laura Miriel, James Tonascia, Frank A. Hamilton, Henry P. Parkman, Pankaj Jay Pasricha, John Clarke, Yale Kim, Linda Nguyen, Nighat Ullah, William Snape, Nata DeVole, Mary Greene, Candice Lee, Courtney Ponsetto, Katerina Shetler, Henry P. Parkman, Steven Kantor, Vanessa Lytes, Amiya Palit, Kellie Simmons, Richard W. McCallum, Reza Hejazi, Kathy Roeser, Irene Sarosiek, Denise Vasquez, Natalia Vega, Thomas Abell, Karen Beatty, Lisa Hatter, Ronna Howard, Lindsay Nowotny, Shou Tang, Om S. Amin, Olivia Henry, Archana Kedar, Valerie McNair, Susanne Pruett, Margaret Smith, Danielle Spree, William Hasler, Michelle Castle, Radoslav Coleski, Sophanara Wootten, Kenneth Koch, Lynn Baxter, Anya Brown, Samantha Culler, Judy Hooker, Paula Stuart, Gianrico Farrugia, Madhusudan Grover, Cheryl Bernard, Jorge Calles-Escandon, Jose Serrano, Frank Hamilton, Steven James, Rebecca Torrance, Rebekah Van Raaphorst, James Tonascia, Patricia Belt, Erin Corless Hallinan, Ryan Colvin, Michele Donithan, Mika Green, Milana Isaacson, Wana Kim, Linda Lee, Patrick May, Laura Miriel, Alice Sternberg, Mark Van Natta, Ivana Vaughn, Laura Wilson, Katherine Yates
Journal: Clinical Gastroenterology and Hepatology (2018)
Workplace gyms and canteens should suit doctors’ working patterns, says BMA report
Authors: Abi Rimmer
Journal: BMJ (2018)

Inequality of access affects workplace health and wellbeing services, the BMA has said in a report that calls for more flexible opening hours to accommodate doctors’ working patterns.1

The report on supporting health and wellbeing at work found that NHS pressures, including underfunding, workforce shortages, and rising patient demand, were affecting doctors’ mental and physical wellbeing.

It urged trusts and health boards to review their current funding and commissioning of health and wellbeing services to ensure that they meet doctors’ …
Clinical course of patients with metastatic papillary renal cell carcinoma
Authors: T. Steiner, J. Roigas, H. Kirchner, C. Doehn, H. Heynemann, M. Siebels, S. Loening, D. Jocham, P. Fornara, D. Rohde, C. G. Stieff
Journal: Journal of Clinical Oncology (2006)

14591 Background: For a long time it has been discussed, whether patients (pts.) with metastatic papillary renal cell carcinoma (mRCC pap) demonstrate different behaviour compared to those with clear cell mRCC. Methods: Clinical data of 61 pts. with mRCC pap were retrospectively assessed at 8 treatment centres. Results: Median follow-up was 20 (1–114) months, median age at time of diagnosis was 62 (24–85) years. Men were affected predominantly (50/61 pts.; 82%). 21 pts. (34%) showed metastases at time of diagnosis. The remaining 40 pts. had metachroneous metastatic disease. Mean time to metastases development was 30.4 (3–143; median 16.5) months. Metastatic sites were: lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%). Local recurrences occurred in 17 pts. (28%). Others sites of metastatic disease were brain in 6 pts. (10%), peritoneal carcinosis in 5 pts. (8%) and others. A surgical approach was performed primarily in 11 pts. (18%): lung 2; local recurrence and lymphomas 7; liver 1; brain 1. 26/61 pts. with metastatic disease received an immuno- (interferon-a ± interleukin-2) or immunochemotherapy (in combination with vinblastine or 5-fluorouracile) as first line treatment. In total, 42/61 pts. (69%) received an interferon- or interleukin-based immunotherapy. No treatment at all was performed in 12 pts. (20%) because of poor performance status. 5/42 pts. (11.4%) achieved an objective response to immuno(chemo)therapy. In the Kaplan-Meier-analysis, median overall survival after diagnosis of metastatic disease was estimated to be 13 ± 1.5 (95% CI 9.9–16) months for the entire study group and 12 ± 2.5 (95% CI 7.1–16.3) from the beginning of systemic treatment. Conclusions: Clinical data of a large population of pts. with mRCC pap have been assessed in this retrospective analysis for the first time. Compared to pts. with clear cell mRCC, these patients are characterized by: I) more frequent local recurrences; II) lower remission rates to immuno(chemo)therapeutic approaches; III) poorer prognosis with regard to overall survival. These findings should be taken into account when planning future studies. No significant financial relationships to disclose.
Tumor microenvironment-manipulated radiocatalytic sensitizer based on bismuth heteropolytungstate for radiotherapy enhancement
Authors: Ruyi Zhou, Huamei Wang, Yufei Yang, Chenyang Zhang, Xinghua Dong, Jiangfeng Du, Liang Yan, Guangjin Zhang, Zhanjun Gu, Yuliang Zhao
Journal: Biomaterials (2018)
Abstract 17624: MRTF-A Mediates Development of Aortic Dissection Through Aortic Smooth Muscle Cell Apoptosis and Inflammatory Response
Authors: Sohei Ito, Hiroki Aoki, Michihide Nishihara, Satoko Ohno, Aya Furusho, Saki Hirakata, Norifumi Nishida, Makiko Hayashi, Yoshihiro Fukumoto
Journal: Circulation (2017)

Aortic dissection (AD) is the major aortic disease with poor outcome. AD seems to be triggered by the mechanical stress on aortic walls, presumably by inducing excessive inflammatory response and d...
RefSeq database growth influences the accuracy of k-mer-based lowest common ancestor species identification
Authors: Daniel J. Nasko, Sergey Koren, Adam M. Phillippy, Todd J. Treangen
Journal: Genome biology (2018)

In order to determine the role of the database in taxonomic sequence classification, we examine the influence of the database over time on k-mer-based lowest common ancestor taxonomic classification. We present three major findings: the number of new species added to the NCBI RefSeq database greatly outpaces the number of new genera; as a result, more reads are classified with newer database versions, but fewer are classified at the species level; and Bayesian-based re-estimation mitigates this effect but struggles with novel genomes. These results suggest a need for new classification approaches specially adapted for large databases.
A Miniaturized, Programmable Pacemaker for Long-Term Studies in the Mouse
Authors: Maarten Hulsmans, Aaron D. Aguirre, Matthew D. Bonner, Aneesh Bapat, Sebastian Cremer, Yoshiko Iwamoto, Kevin R. King, Filip K. Swirski, David J. Milan, Ralph Weissleder, Matthias Nahrendorf
Journal: Circulation Research (2018)

Cardiac pacing is a critical technology for the treatment of arrhythmia and heart failure. The impact of specific pacing strategies on myocardial function is an area of intense research and high clinical significance. Mouse models have proven extremely useful for probing mechanisms of heart disease, but there is currently no reliable technology for long-term pacing in the mouse.We sought to develop a device for long-term pacing studies in mice. We evaluated the device for (1) treating third-degree atrioventricular block after macrophage depletion, (2) ventricular pacing-induced cardiomyopathy, and (3) high-rate atrial pacing.We developed a mouse pacemaker by refashioning a 26 mm×6.7 mm clinical device powered by a miniaturized, highly efficient battery. The electrode was fitted with a single flexible lead, and custom software extended the pacing rate to up to 1200 bpm. The wirelessly programmable device was implanted in the dorsal subcutaneous space of 39 mice. The tunneled lead was passed through a left thoracotomy incision and attached to the epicardial surface of the apex (for ventricular pacing) or the left atrium (for atrial pacing). Mice tolerated the implantation and both long-term atrial and ventricular pacing over weeks. We then validated the pacemaker's suitability for the treatment of atrioventricular block after macrophage depletion in Cd11b DTR mice. Ventricular pacing increased the heart rate from 313±59 to 550 bpm ( P<0.05). In addition, we characterized tachypacing-induced cardiomyopathy in mice. Four weeks of ventricular pacing resulted in reduced left ventricular function, fibrosis, and an increased number of cardiac leukocytes and endothelial activation. Finally, we demonstrated the feasibility of chronic atrial pacing at 1200 bpm.Long-term pacing with a fully implantable, programmable, and battery-powered device enables previously impossible investigations of arrhythmia and heart failure in the mouse.
Beet the Best?
Authors: Mary Woessner, Mitch D. VanBruggen, Carl F. Pieper, Richard Sloane, William E. Kraus, Andrew J. Gow, Jason D. Allen
Journal: Circulation Research (2018)

Rationale: A primary goal of therapy for patients with peripheral artery disease (PAD) and intermittent claudication is increased ambulatory function. Supervised exercise rehabilitation was recently shown to confer superior walking benefits to pharmacological or surgical interventions. Increases in plasma inorganic nitrite, via oral nitrate, have been shown to increase exercise performance in both human and animal models, especially in hypoxic conditions. Objective: To determine whether a 36-session exercise rehabilitation program while consuming oral inorganic nitrate (4.2 mmol concentrated beetroot juice) would produce superior benefits over exercise plus placebo in pain-free walking and markers of increased skeletal muscle perfusion in patients with PAD and intermittent claudication. Methods and Results: This was a randomized, double-blind, per-protocol study design. After the 12-week protocol, claudication onset time on a maximal treadmill test increased by 59.2±57.3 s for the exercise plus placebo group (n=13) and by 180.3±46.6 s for the exercise plus beetroot juice group (n=11; P ≤0.05). This produced a between treatment medium to large standardized effect size (Cohen d) of 0.62 (95% CI, −0.23 to +1.44). The data for 6-minute walk distance showed a similar pattern with increases of 24.6±12.1 and 53.3±19.6 m ( P ≤0.05) in the exercise plus placebo and exercise plus beetroot juice groups, respectively. Measures of gastrocnemius perfusion, including ankle-brachial index, peak reactive hyperemic blood flow, and tissue deoxygenation characteristics, during exercise (assessed my near-infrared spectroscopy) all changed significantly for the exercise plus beetroot juice group with moderate-to-large effect sizes over exercise plus placebo changes. Conclusions: Although it is premature to speculate on overall clinical utility of a nitrate-based therapy for PAD, this early pilot study evidence is encouraging. Specifically, our data suggests that increasing plasma nitrite before exercise may allow PAD subjects to train with less pain, at higher workloads for longer durations at each training session, thereby maximizing the beneficial peripheral vascular and skeletal muscle adaptations. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01684930 and NCT01785524.
The digital scribe
Authors: Enrico Coiera, Baki Kocaballi, John Halamka, Liliana Laranjo
Journal: npj Digital Medicine (2018)

Current generation electronic health records suffer a number of problems that make them inefficient and associated with poor clinical satisfaction. Digital scribes or intelligent documentation support systems, take advantage of advances in speech recognition, natural language processing and artificial intelligence, to automate the clinical documentation task currently conducted by humans. Whilst in their infancy, digital scribes are likely to evolve through three broad stages.
Progression-free survival and recurrence results for AGITG DOCTOR: Pre-op cisplatin, 5FU &amp; DOCetaxel +/-radiotherapy after poor early response to cisplatin &amp; 5FU for resectable oesophageal adenocarcinoma
Authors: A.P. Barbour, E.T. Walpole, G.T. Mai, L. Barnes, D.I. Watson, S.P. Ackland, V. Wills, J. Martin, M. Burge, C.S. Karapetis, J. Shannon, L.M. Nott, V. Gebski, M. Oostendorp, K. Wilson, J. Thomas, G. Lampe, J.R. Zalcberg, J. Simes, M. Smithers
Journal: Annals of Oncology (2018)
Abstract 17877: Overexpression of the H2S Producing Enzyme Cystathionine gamma-Lyase in Endothelial Cells Ameliorates Myocardial Ischemia/Reperfusion Injury
Authors: Zhen Li, Chelsea L Organ, Erminia Donnarumma, Craig M Zibilich, John W Elrod, David J Lefer
Journal: Circulation (2016)

Background: Hydrogen sulfide (H2S) donors protect against acute myocardial ischemia/reperfusion (MI/R) injury. Cystathionine gamma-lyase (CSE) is one of three H2S producing enzymes that regulate H2S bioavailability. We have previously demonstrated that overexpression of CSE in myocardium protects against MI/R injury. Objective: The purpose of this study was to investigate if endothelial cell restricted overexpression of CSE protects the myocardium against I/R injury. Methods and Results: Endothelial cell specific CSE transgenic (EC-CSE Tg) mice were generated by crossing the mice carrying the CSE gene driven by tetracycline response element to the mice with VE-Cadherin-driven tTA gene. EC-CSE Tg mice and tTA control mice (n = 7-9 per group) were sacrificed. Plasma free H2S level were determined with gas chromatography and sulfur chemiluminescence (Aligent). Significantly elevated plasma free H2S level were observed in EC-CSE Tg mice (0.28 ± 0.02 vs. 0.15 ± 0.04 μM, p < 0.05). EC-CSE Tg mice, tTA control m...
Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study
Authors: Jianming Xu, Yun Zhang, Ru Jia, Chunyan Yue, Lianpeng Chang, Rongrui Liu, Gairong Zhang, Chuanhua Zhao, Yaoyue Zhang, Chunxia Chen, Yan Wang, Xin Yi, Zhiyuan Hu, Jianjun Zou, Quanren Wang
Journal: Clinical Cancer Research (2018)

Abstract Purpose: This study assessed the safety and efficacy of SHR-1210 (anti-PD-1 antibody) and apatinib (VEGFR2 inhibitor) as combination therapy in patients with advanced hepatocellular carcinoma (HCC), gastric, or esophagogastric junction cancer (GC/EGJC). Patients and Methods: This was an open-label, dose-escalation (phase Ia) and expansion study (phase Ib). In phase Ia, patients (n = 15) received SHR-1210 200 mg every 2 weeks and apatinib 125–500 mg once daily until unacceptable toxicity or disease progression. In phase Ib, patients (n = 28) received apatinib at the phase Ia–identified recommended phase II dose (RP2D) plus SHR-1210. The primary objectives were safety and tolerability and RP2D determination. Results: At data cutoff, 43 patients were enrolled. In phase Ia, four dose-limiting toxicity events were observed (26.7%): one grade 3 lipase elevation (6.7%) in the apatinib 250 mg cohort and three grade 3 pneumonitis events (20%) in the apatinib 500 mg cohort. The maximum tolerated RP2D for apatinib was 250 mg. Of the 33 patients treated with the R2PD combination, 20 (60.6%) experienced a grade ≥3 treatment-related adverse event; adverse events in ≥10% of patients were hypertension (15.2%) and increased aspartate aminotransferase (15.2%). The objective response rate in 39 evaluable patients was 30.8% (95% CI: 17.0%–47.6%). Eight of 16 evaluable HCC patients achieved a partial response (50.0%, 95% CI: 24.7%–75.4%). Conclusions: SHR-1210 and apatinib combination therapy demonstrated manageable toxicity in patients with HCC and GC/EGJC at recommended single-agent doses of both drugs. The RP2D for apatinib as combination therapy was 250 mg, which showed encouraging clinical activity in patients with advanced HCC.
GW29-e0548 Effect and cost-effectiveness of promoting statins use in primary prevention of atherosclerotic cardiovascular disease control in China: A predictive study base on Chinese multi-provincial cohort study
Authors: Miao Wang, Jing Liu, Wei Wang, Yue Qi, Jun Liu, Jiayi Sun, Yongchen Hao, Lanpiing Qin, Dong Zhao
Journal: Journal of the American College of Cardiology (2018)
Re: Melissa Assel, Anders Dahlin, David Ulmert, et al. Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening. Eur Urol 2018;73:961–7
Authors: Kathryn L. Penney, Massimo Loda, Meir J. Stampfer
Journal: European Urology (2018)
C5a receptor 1<sup>−/−</sup> mice are protected from the development of IgE‐mediated experimental food allergy
Authors: Anna Kordowski, Anna T. Reinicke, David Wu, Zane Orinska, Philipp Hagemann, Markus Huber‐Lang, Jee‐Boong Lee, Yui‐Hsi Wang, Simon P. Hogan, Jörg Köhl
Journal: Allergy (2018)

Food-induced anaphylaxis is a serious allergic reaction caused by Fcε-receptor activation on mast cells (MCs). The exact mechanisms breaking oral tolerance and the effector pathways driving food allergy remain elusive. As complement is activated in food-induced anaphylaxis, we aimed to assess the role of C5a in disease pathogenesis.
The accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy in clinically node positive breast cancer patients: A single institution experience
Authors: N. Sistany Allahabadi, H. Yahyazadeh, M. Hashemian, M. Rajabpour, S. Aminmozaffari, M. Zaree, A. Rezazadeh Mafi
Journal: Annals of Oncology (2018)
Natural History of Diabetic Coronary Atherosclerosis by Quantitative Measurement of Serial Coronary Computed Tomographic Angiography
Authors: Ung Kim, Jonathon A. Leipsic, Stephanie L. Sellers, Michael Shao, Philipp Blanke, Martin Hadamitzky, Yong-Jin Kim, Edoardo Conte, Daniele Andreini, Gianluca Pontone, Matthew J. Budoff, Ilan Gottlieb, Byoung Kwon Lee, Eun Ju Chun, Filippo Cademartiri, Erica Maffei, Hugo Marques, Sanghoon Shin, Jung Hyun Choi, Renu Virmani, Habib Samady, Peter H. Stone, Daniel S. Berman, Jagat Narula, Leslee J. Shaw, Jeroen J. Bax, James K. Min, Hyuk-Jae Chang
Journal: JACC. Cardiovascular imaging (2018)