tbuckley/cabot-search huggingface dataset:
DETERMINING THE RISKS OF MAGNETIC RESONANCE IMAGING AT 1.5 TESLA FOR PATIENTS WITH PACEMAKERS AND IMPLANTABLE CARDIOVERTER DEFIBRILLATORS: THE MAGNASAFE REGISTRY
Authors: Robert J. Russo, Heather Costa, Ashish Kabra, Debra Doud, Seth Uretsky, Steven Wolff, Edward Martin, Christian Machado, Steven Higgins, Gail Tominaga, Todd Florin, Daniel Bloomgarden, Ulrika Birgersdotter-Green, George Ponce, Raymond Schaerf, Rachel Lampert, Dipan Shah, Aysha Arshad, Jeffrey Anderson, Allison Tonkin, Andrew Rivard, Frazier Fyke, Robert Biederman
Journal: Journal of the American College of Cardiology (2013)
Surgical treatment of hepatocellular carcinoma with advanced portal vein tumor thrombus combined with pre-operative radiotherapy.
Authors: Kenji Wakayama, Toshiya Kamiyama, Tatsuya Orimo, Akihisa Nagatsu, Shingo Shimada, Hideki Yokoo, Hirofumi Kamachi, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2018)

385 Background: Hepatocellular carcinoma (HCC) with advanced portal vein tumor thrombus (PVTT) in the main portal trunk (MPT) or the first branch of portal vein has poor prognosis. We attempted a multidisciplinary treatment to irradiate the PVTT prior to surgical resection. In this study, we evaluate the therapeutic effect of preoperative radiotherapy (Pre-RT) for HCC with advanced PVTT. Methods: The postoperative prognosis was retrospectively examined in 75 patients with advanced PVTT out of 1,045 patients who underwent hepatectomy for HCC between 1990 and 2015 in our institute. The treatment outcome was compared between the patients who underwent Pre-RT (30Gy/10fr) for PVTT before operation (RT group, n = 34) and patients not underwent Pre-RT (non-RT group, n = 41). Results: Among 75 patients with advanced PVTT, there was no difference in age, sex, extent of PVTT (MPT or first branch of PV), HBV, HCV, T-Bil, PT(%), ICG R15%, Child-Pugh classification, AFP, DCP, intra-operative blood loss, tumor size, tumor number, coexisting hepatic vein or bile duct tumor thrombus, presence of the residual tumor between RT and non-RT group other than adjuvant chemotherapy administration (p = 0.0009). The 5-year overall survival rate of all 75 cases was 18.5%. There was a significant overall survival extension in RT group with 29.4% compared to 16.2% in non-RT group (p = 0.039, log-rank test). Surgery without residual lesions was performed in 64 patients, of which the 5-year recurrence-free survival rate was 10.9%. The 5-year recurrence-free survival rate of RT group (n = 30) (16.1%) was significantly better than non-RT group (n = 34) (5.5%) (p = 0.027, log-rank test). Univariate analysis using Cox proportional hazard model demonstrated that the Pre-RT was the only significant prognostic factor (HR 0.595, 95% CI 0.356 - 0.981, p = 0.042) for overall survival, and the Pre-RT and tumor size over 10cm for recurrence-free survival among these patient’s factors. Conclusions: Multidisciplinary treatment combined preoperative radiotherapy to PVTT and subsequent surgical resection improve the prognosis for the patients of HCC with advanced PVTT extend to MPT or first branch of PV.
Dynamic monitoring HER2 amplification of circulating DNA in metastatic colorectal cancer patients treated with cetuximab.
Authors: Zhi-Yu Chen, Rujiao Liu, Weijian Guo, Xiaodong Zhu, Xiaoying Zhao, Lixin Qiu, Xiaowei Zhang, Mingzhu Huang, Wen Zhang, Zhe Zhang, Wenhua Li
Journal: Journal of Clinical Oncology (2018)

714 Background: Addition of cetuximab has shown clinical benefit in RAS and BRAF wild-type (wt) patients with metastatic colorectal cancer (mCRC). Human epidermal growth factor receptor 2 ( HER2) amplification was reported to be one of the resistance mechanisms to cetuximab. We investigated whether monitoring of HER2 amplification in circulating DNA allows early detection of progression and informs about resistance to cetuximab. Methods: We analyzed HER2 amplification in circulating DNA by 8 week-interval using droplet digital polymerase chain reaction (ddPCR) from 30 RAS and BRAF wt patients, who progressed after failure of cetuximab-containing regimens between Jul 2015 and Jun 2017. Results: 16.7% (5/30) of patients exhibited dynamic fluctuations of HER2 amplification in plasma, one of whom was found to be positive for HER2 amplification in matched tumor tissue sample using FISH. Two patients had HER2 and c-MET co-amplification. All 5 primary sites were left side, 4 rectums and 1 descending colon. 3 patients received cetuximab as first line therapy, whereas 2 patients in the 2 nd line setting. Among these 5 patients, changes in circulating DNA levels showed good agreement with changes in tumor volume. Furthermore, quantifications of HER2 amplification showed obvious increase with an average lead time of 2 months compared with CT documented progress. But interestingly, there was no difference in progression-free survival (PFS) between these 5 patients and the others without HER2 amplification (p &gt; 0.05). Conclusions: Plasma HER2 amplification detected by ddPCR was showed dynamic changing over time and would predict resistance to cetuximab-containing treatment. Average 2 months lead time was observed and need to validate in the further study.
Collaborating agents: Values, sociality, and moral responsibility
Authors: John M Doris
Journal: Behavioral and Brain Sciences (2018)

Abstract I respond to the Behavioral and Brain Sciences commentaries on my book, Talking to Our Selves: Reflection, Ignorance, and Agency . I defend and amend both the skeptical challenge to morally responsible agency, that is, the book's impetus, and the anti-skeptical theory I develop to address that challenge. Regarding the skeptical challenge, I argue that it must be taken more seriously than some of my sanguine commentators assert, and consider some ways its impact might be blunted, such as by appeal to individual differences and the practical efficacy of human behavior. Regarding my positive theory, I defend the role of values in morally responsible agency against numerous criticisms, and consider various suggestions for elaborating my social, “collaborativist” account of morally responsible agency. In closing, I comment on the appropriate aspirations for theorizing about moral responsibility and agency.
Suppression of poly-ADP ribose (PAR) levels in PBMCs by veliparib (vel) as a pharmacodynamic (PD) marker associated with survival among women with BRCA1- or BRCA2- (BRCA)-associated metastatic breast cancer (MBC).
Authors: Jeffrey N. Weitzel, Paul Henry Frankel, Josef Herzog, Banu Arun, Jan Hendrik Beumer, Cynthia X. Ma, Tessa Cigler, Leah Cream, Harold A. Harvey, Joseph A. Sparano, Rita Nanda, Helen K. Chew, Linda T. Vahdat, Matthew P. Goetz, David R. Gandara, Richard Piekarz, Lily Ravel Van Tongeren, Katherine V. Ferry-Galow, Timothy W. Synold, George Somlo
Journal: Journal of Clinical Oncology (2016)

2549 Background: PARP inhibitor therapy of BRCA-associated cancer exploits the concept of synthetic lethality, yet there have been limited PD markers of efficacy. We report here on baseline PAR and suppression of PAR in PBMCs as a PD marker of clinical outcome, as well as pharmacokinetics (PK). Methods: Pts received either carboplatin (carb) IV and oral vel (Phase I) or single agent vel (Phase II) followed by post-progression therapy with the combination (NCI protocol #8264; NO1-CM-2011-00038). Blood for PK analysis (phase I only) and PBMCs were collected at baseline, at 3hrs, and at additional later time points. Plasma vel and PAR were quantitated using LC-MS assay and CTEP-validated reagents and methods, respectively. Results: 72 evaluable pts included 28 in Phase I, 44 in Phase II. PK samples were available for 25/28 pts in phase I; vel PK parameters are in line with values previously reported (Cl/F 20.9 L/h, V/F 173 L, t1/2 6.1 h). Response rate (RR) in phase I was 56% [CR rate 15%] and 3 remain in CR at 39, 42, and 46 months (2 on vel maintenance, 1 is off therapy). Paired baseline and 3 hr PBMC samples for PAR levels were available for 50 pts (18 phase I, 32 phase II). Higher baseline PAR levels (as a continuous variable) predict for better TTF (p < 0.01) and OS (p < 0.04), with marginal significance in PFS (p = 0.05) in Phase I patients. Using the median baseline PAR level from Phase I pts as a cut-point, there was increased hazard for the low PAR group (HR = 4.21 [1.39-12.8] in Phase I for TTF, and 2.1 [0.84-5.03] for Phase II). OS was worse for low PAR in both Phase I (HR = 2.75 [1.0-7.6]) and Phase II (HR = 3.7 [1.3-10.4]). Pts whose PAR level was reduced by more than 50% at 3 hrs also showed improved outcome. In multivariate analysis (including triple negativity, BRCA2 vs BRCA1, no. of sites, visceral disease, no. of prior Rx, ER/PR and age) only PAR (either the 50% reduction in PAR or baseline PAR < median, but not both as they were highly inversely correlated), was retained in the final prediction model for OS and TTF. Conclusions: Baseline level and reduction of PAR after treatment with vel associates with outcome among women with BRCA-associated MBC. Clinical trial information: NCT01149083.
Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function
Authors: Jakub Otwinowski
Journal: Molecular Biology and Evolution (2018)

Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish whether mutations directly affect function or are destabilizing the protein. Here, we introduce a statistical method to infer the underlying biophysics from a high-throughput binding assay by combining information from many mutated variants. We fit a thermodynamic model describing the bound, unbound, and unfolded states to high quality data of protein G domain B1 binding to IgG-Fc. We infer an energy landscape with distinct folding and binding energies for each substitution providing a detailed view of how mutations affect binding and stability across the protein. We accurately infer folding energy of each variant in physical units, validated by independent data, whereas previous high-throughput methods could only measure indirect changes in stability. While we assume an additive sequence-energy relationship, the binding fraction is epistatic due its non-linear relation to energy. Despite having no epistasis in energy, our model explains much of the observed epistasis in binding fraction, with the remaining epistasis identifying conformationally dynamic regions.
Abstract 17421: Vector Flow Mapping Quantification of Left Ventricular Energy Loss Occurring in Normal Subjects
Authors: Masataka Sugahara, Zhi Qi, Tijmen Koopsen, Marc D Simon, John Gorcsan
Journal: Circulation (2016)

Introduction: Vector flow mapping (VFM) can uniquely quantify left ventricular (LV) flow dynamics non-invasively. Energy loss produced by turbulent flow has promise to characterize cardiovascular d...
SPARC: A phase-I trial of pre-operative margin-intensified stereotactic radiotherapy for pancreatic cancer at high risk of positive resection margins.
Authors: Daniel Holyoake, Maxwell Robinson, Victoria Y Strauss, Gavin Reilly, David McIntosh, Derek B Grose, Ganesh Radhakrishna, David Sebag-Montefiore, Somnath Mukherjee, Maria A Hawkins
Journal: Journal of Clinical Oncology (2018)

TPS536 Background: Standard therapy for resectable and borderline resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but clear resection margins rates are unsatisfactory. Conventional neoadjuvant radiotherapy has limited efficacy, but stereotactic radiotherapy (SBRT) achieves accuracy and precision to enable dose escalation and margin-intensification, with the goal of achieving clear resection margins. This prospective multi-centre study aims to establish the maximum tolerated dose of margin-intensified pre-operative SBRT, for subsequent definitive comparison with other neoadjuvant treatment options. Methods: SPARC is a phase-I dose-escalation study (NCT02308722). A ‘rolling-six’ design is utilised to minimise delays and facilitate ongoing recruitment during dose escalation. Eligibility comprises histologically or cytologically proven borderline-resectable pancreatic cancer, or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres. Radiotherapy is delivered in 5 daily fractions, with surgery planned to take place 5–6 weeks later. The margin-intense radiotherapy concept utilises a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration. Up to 4 radiotherapy dose levels will be investigated, and the maximum tolerated dose is the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival, and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to SBRT in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015 and eleven patients have been treated to date. Cohort 1 was completed without DLT and recruitment to cohort 2 began in September 2016. Clinical trial information: NCT02308722.
Radiation induces age-dependent deficits in cortical synaptic plasticity
Authors: Die Zhang, Wei Zhou, Thanh Thai Lam, Connie Weng, Lawrence Bronk, Duo Ma, Qiang Wang, Joseph G Duman, Patrick M Dougherty, David R Grosshans
Journal: Neuro-Oncology (2018)

Radiation-induced cognitive dysfunction is a significant side effect of cranial irradiation for brain tumors. Clinically, pediatric patients are more vulnerable than adults. However, the underlying mechanisms of dysfunction, including reasons for age dependence, are still largely unknown. Previous studies have focused on the loss of hippocampal neuronal precursor cells and deficits in memory. However, survivors may also experience deficits in attention, executive function, or other non-hippocampal–dependent cognitive domains. We hypothesized that brain irradiation induces age-dependent deficits in cortical synaptic plasticity. In vivo recordings were used to test neuronal plasticity along the direct pathway from the cornu ammonis 1 (CA1)/subicular region to the prefrontal cortex (PFC). Specifically, long-term potentiation (LTP) in the CA1/subicular-PFC pathway was assessed after cranial irradiation of juvenile and adult Sprague Dawley rats. We further assessed a potential role for glutamate toxicity by evaluating the potential neuroprotective effects of memantine. LTP was greatly inhibited in both adult and juvenile animals at 3 days after radiation but returned to near-normal levels by 8 weeks—only in adult rats. Memantine given before, but not after, irradiation partially prevented LTP inhibition in juvenile and adult rats. Cranial radiation impairs neuroplasticity along the hippocampal–PFC pathway; however, its effects vary by age. Pretreatment with memantine offered protection to both juvenile and adult animals. Deficits in cortical plasticity may contribute to radiation-induced cognitive dysfunction, including deficits in attention and age-dependent sensitivity of such pathways, which may underlie differences in clinical outcomes between juveniles and adults after cranial irradiation.
Practical Guide to Surgical Data Sets: Surveillance, Epidemiology, and End Results (SEER) Database
Authors: Kemi M. Doll, Alfred Rademaker, Julie A. Sosa
Journal: JAMA Surgery (2018)

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Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update
Authors: Kutluk Oktay, Brittany E. Harvey, Ann H. Partridge, Gwendolyn P. Quinn, Joyce Reinecke, Hugh S. Taylor, W. Hamish Wallace, Erica T. Wang, Alison W. Loren
Journal: Journal of Clinical Oncology (2018)

Purpose To provide current recommendations about fertility preservation for adults and children with cancer. Methods A systematic review of the literature published from January 2013 to March 2017 was completed using PubMed and the Cochrane Library. An Update Panel reviewed the identified publications. Results There were 61 publications identified and reviewed. None of these publications prompted a significant change in the 2013 recommendations. Recommendations Health care providers should initiate the discussion on the possibility of infertility with patients with cancer treated during their reproductive years or with parents/guardians of children as early as possible. Providers should be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, providers should advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm, oocyte, and embryo cryopreservation are considered standard practice and are widely available. There is conflicting evidence to recommend gonadotrophin-releasing hormone agonists (GnRHa) and other means of ovarian suppression for fertility preservation. The Panel recognizes that, when proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. GnRHa should not be used in place of proven fertility preservation methods. The panel notes that the field of ovarian tissue cryopreservation is advancing quickly and may evolve to become standard therapy in the future. Additional information is available at www.asco.org/survivorship-guidelines .
A Silk Cranial Fixation System for Neurosurgery
Authors: Keyin Liu, Zhifeng Shi, Shaoqing Zhang, Zhitao Zhou, Long Sun, Tao Xu, Yeshun Zhang, Guozheng Zhang, Xinxin Li, Liang Chen, Ying Mao, Tiger H. Tao
Journal: Advanced Healthcare Materials (2018)

Cranial fixation should be safe, reliable, ideally degradable, and produce no hazardous residues and no artifacts on neuroimaging. Protein-based fixation devices offer an exciting opportunity for this application. Here, the preclinical development and in vivo efficacy verification of a silk cranial fixation system in functional models are reported by addressing key challenges toward clinical use. A comprehensive study on this fixation system in rodent and canine animal models for up to 12 months is carried out. The silk fixation system shows a superb performance on the long-term stability of the internal structural support for cranial flap fixation and bone reconnection and has good magnetic resonance imaging compatibility, and tolerability to high dose radiotherapy, underscoring the favorable clinical application of this system for neurosurgery compared to the current gold standard.
Release of targeted protein nanoparticles from functional bacterial amyloids: A death star-like approach
Authors: Ugutz Unzueta, María Virtudes Cespedes, Rita Sala, Patricia Alamo, Alejandro Sánchez-Chardi, Mireia Pesarrodona, Laura Sánchez-García, Olivia Cano-Garrido, Antonio Villaverde, Esther Vázquez, Ramón Mangues, Joaquin Seras-Franzoso
Journal: Journal of Controlled Release (2018)
In vitro biodegradation testing of Mg-alloy EZK400 and manufacturing of implant prototypes using PM (powder metallurgy) methods
Authors: M. Wolff, M. Luczak, J.G. Schaper, B. Wiese, M. Dahms, T. Ebel, R. Willumeit-Römer, T. Klassen
Journal: Bioactive Materials (2018)

The study is focussing towards Metal Injection Moulding (MIM) of Mg-alloys for biomedical implant applications. Especially the influence of the sintering processing necessary for the consolidation of the finished part is in focus of this study. In doing so, the chosen high strength EZK400 Mg-alloy powder material was sintered using different sintering support bottom plate materials to evaluate the possibility of iron impurity pick up during sintering. It can be shown that iron pick up took place from the steel bottom plate into the specimen. Despite the fact that a separating boron nitrite (BN) barrier layer was used and the Mg-Fe phase diagram is not predicting any significant solubility to each other. As a result of this study a new bottom plate material not harming the sintering and the biodegradation performance of the as sintered material, namely a carbon plate material, was found.
Publisher Correction: A craniofacial–specific monosynaptic circuit enables heightened affective pain
Authors: Erica Rodriguez, Katsuyasu Sakurai, Jennie Xu, Yong Chen, Koji Toda, Shengli Zhao, Bao-Xia Han, David Ryu, Henry Yin, Wolfgang Liedtke, Fan Wang
Journal: Nature Neuroscience (2018)
Chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: to screen or not to screen?
Authors: Marius M. Hoeper
Journal: European Respiratory Journal (2018)

How many patients who survive acute pulmonary embolism will eventually develop chronic thromboembolic pulmonary hypertension (CTEPH) and is the risk sufficiently high to call for systematic screening? These two questions are obviously connected and the ongoing debate reflects a lack of robust data. Previous estimates on the incidence of CTEPH after acute pulmonary embolism have ranged from 0.1% [1] to 9.1% [2]; an almost 2-log difference. A widely regarded Italian study of 223 consecutive patients with acute pulmonary embolism found a cumulative CTEPH incidence of 3.8% after 2 years; no additional CTEPH cases were identified during long-term follow-up [3]. In contrast, a more recent series, also from Italy, that included 647 patients with acute embolism found a cumulative CTEPH incidence of 1.7% during a 3-year follow-up [4, 5]. A recent meta-analysis of 41 studies narrowed the numbers down but still provided conflicting results [6]: 0.56% of all patients with acute pulmonary embolism developed CTEPH over a period of 2–3 years; however, in a subset of four studies that included only survivors of acute pulmonary embolism, the CTEPH incidence was 3.2%. As the risk of CTEPH in survivors of acute pulmonary embolism is probably in the range of 0.5–1.0%, screening is unlikely to be efficacious <http://ow.ly/66ov30iWjnY>