tbuckley/cabot-search huggingface dataset:
Realizing the Now-or-Never bottleneck and Chunk-and-Pass processing with Item-Order-Rank working memories and masking field chunking networks
Authors: Stephen Grossberg
Journal: Behavioral and Brain Sciences (2016)

Abstract Christiansen &amp; Chater's (C&amp;C's) key goals for a language system have been realized by neural models for short-term storage of linguistic items in an Item-Order-Rank working memory, which inputs to Masking Fields that rapidly learn to categorize, or chunk, variable-length linguistic sequences, and choose the contextually most predictive list chunks while linguistic inputs are stored in the working memory.
Prospective assessment of dosimetric/physiologic models to predict radiation pneumonitis
Authors: Z. Kocak, D. Kahn, X. Yu, S. Zhou, D. Hollis, T. Shafman, R. Clough, R. J. Folz, A. Tisch, L. B. Marks
Journal: Journal of Clinical Oncology (2004)

7280 Background: A variety of clinical and dosimetric parameters extracted from the 3D dose distribution have been associated with the risk of symptomatic radiation pneumonitis in retrospective studies. Such parameters include the mean lung dose (MLD), the radiation dose distribution relative to functioning perfused lung (assessed by single photon emission computed tomography-SPECT), and the pre-RT lung function (i.e. PFT's). Based on our work and others, we defined pre-RT criteria that we hypothesized would be predictive for the later development of pneumonitis. We herein prospectively test the predictive abilities of these dosimetric/functional parameters. This study was performed on a new cohort of patients, who were not included in our analyses that defined the predictive models. Methods: Between 1999–2003, 63 patients receiving thoracic RT for lung cancer were enrolled onto a prospective IRB-approved study to monitor RT-induced lung injury. 37 patients without evidence of recurrent intra-thoracic tumor after >6 months post-RT were included in this analysis. Patients at high and low risk for pneumonitis were defined based on: a) the mean lung dose, b) the 3D dose distribution relative to the pre-RT SPECT lung perfusion scan, and c) the pre-RT DLCO. The rates of pneumonitis in the high and low risk groups were compared using Fisher's exact test. The areas under receiver operating characteristic (ROC) curves were used to compare alternative predictive models. Results: Pneumonitis rates in the patients predicted to be at high vs. low risk were similar. For the overall patient population, the ROC areas provided by the different models were similar and suboptimal (<0.6). No model provided a statistically significant segregation of the patients. Conclusions: Segregating patients into high and low risk groups for pneumonitis is challenging. While the models do have some predictive value, their ROC areas are far from ideal. Additional work is needed to better identify predictors of RT-induced lung injury. Supported by NIH R01 Grant CA69579. Thanks to UNC for PLUNC software. No significant financial relationships to disclose.
Use of Rituximab As a Pre-Emptive Therapy for Epstein-Barr Virus (EBV)-Associated Lymphoproliferative Disorders in 86 Adult Patients Having Allogeneic Stem Cell Transplantation
Authors: Sophie Auger, Mattea Orsini, Nathalie Fegueux, Patrice Ceballos, Marie Luce Mines, Jean-Francois Rossi
Journal: Blood (2011)
Comparison of anemia outcomes associated with early response to epoetin alfa (EPO) withQW and TIW dosing
Authors: R. S. McKenzie, P. Lefebvre, J. Rosberg, M. S. Duh, J. Fastenau, C. T. Piech
Journal: Journal of Clinical Oncology (2004)

6141 Background: Anemia is a common side effect in patients receiving myelosuppressive chemotherapy. This study evaluates whether patients (pts) experiencing an early EPO response (at least 1g/dL hemoglobin (Hb) rise at 4 weeks independent of transfusion in the prior 28 days) had better clinical outcomes by end of study (EOS) compared with late/non-responders (<1g/dL Hb increase at 4 weeks). Methods: Data sets from three 16-week EPO multicenter clinical trials were used (EPO 1: N=2,964; EPO 2: N=681, EPO 3: N=2,289). In EPO 1 and 2, pts received 40,000 U QW with potential for escalation to 60,000 U; in EPO 3, pts received 10,000 U TIW with potential escalation to 20,000 U TIW. Study pts were adults who had a baseline Hb of less than or equal to 11g/dL, and received chemotherapy with or without radiotherapy for treatment of nonmyeloid malignancies. Outcomes included change in quality of life (QoL) measured by Linear Analog Scale Assessment and Functional Assessment of Cancer Therapy -Anemia and Fatigue (latter available for EPO 1 and EPO 3), transfusion use and Hb response (Hb rise of at least 2g/dL independent of transfusion ) between Week 5 and EOS. Results: Early response was observed in 47.1%, 48.9%, and 51.8% of pts from EPO 1, 2, and 3 respectively. Both intent-to-treat and on-treatment analyses yielded similar results, indicating early responders had significantly higher mean change scores than late/non-responders by EOS across all QoL instruments, after controlling for age, gender, tumor type, baseline ECOG score, baseline QoL score, change in Hb after Week 4, tumor response, and chemotherapy. Transfusion use was significantly lower for early responders than for late/non-responders (EPO 1: 5.1% vs. 20.3%, EPO 2: 7.6% vs. 20.1%, EPO 3 7.7% v. 26.8%, all p<0.0001). Hb response was significantly higher for early responders compared to late/non-responders (EPO 1: 84.0% vs. 46.5%, EPO 2: 79.1% vs. 49.1%, EPO 3: 79.8% v. 43.6%; all p<0.0001). Conclusions: Early response with EPO compared to late/non-response was associated with statistically higher changes in QoL, lower transfusion use and higher hemoglobin response by EOS regardless of QW or TIW EPO administration. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Ortho Biotech Products, L.P. Ortho Biotech Products, L.P.
The role of panendoscopy in the staging of high risk head &amp; neck squamous cell carcinoma prior to therapy: Is it of value?
Authors: T. Bhandari
Journal: Journal of Clinical Oncology (2006)

5569 Background: Panendoscopy (triple endoscopy) has historically been advocated to adequately stage patients w/ head &amp; neck squamous cancer, especially in the setting of neoadjuvant therapy. This role is controversial by in view of comparable information provided by current imaging techniques Objective: The primary objective was to analyze the results of panendoscopy in a series of patients enrolled in a neoadjuvant chemo radiation protocol. Methods: We reviewed the panendoscopy results of 69 pts w/ stage III/IV head &amp; neck squamous cell carcinoma (H&amp;N ca) treated w/ neoadjuvant chemo radiation at a single institution from 1996–2005. All pts had detailed laryngoscopy/microlaryngoscopy w/ strategic biopsies, esophago-duodeno-scopy (selected biopsies for Barretts) &amp; placement of percutaneous gastrostomy (PEG) &amp; bronchoscopy washings for cytology. Pts were initially treated w/chemo radiation protocols (H&amp;N 53,67); subsequent protocols utilized induction chemotherapy/chemo radiation (H&amp;N 79,86). Results: Two of 69 pts had malignant cells in bronchial cytology in absence of any lung findings (both were NED at 5 yrs). A radiologically occult primary bronchial cancer was found in an additional pt excluding pt from the protocol. Two pts were diagnosed w/ Barrett’s esophagus; another pt also had a synchronous primary cancer of the cervical esophagus. Nine of 69 pts underwent panendoscopy for cervical metastases from an apparent unknown primary ca (at initial diagnosis). The primary cancer was demonstrated in 6 pts at staging panendoscopy and in another patient at follow up panendoscopy. Conclusion: Panendoscopy is essential in staging high risk H &amp; N ca pts prior to initiation of therapy. A detailed laryngoscopy (micro-laryngoscopy) w/ strategic biopsies is required for adequate staging of all cancers of oropharynx &amp; larynx. Esophago-gastro-duodenoscopy had a low but definable yield, but is also necessary for PEG placement to ensure adequate nutrition during neoadjuvant therapy. Bronchoscopy has a limited role in the absence of radiologic chest findings. No significant financial relationships to disclose.
CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS
Authors: S R Oruganti, D J Torres, S Krebsbach, F Asperti-Boursin, J Winters, K Matlawska-Wasowska, S S Winter, C Halsey, J L Cannon
Journal: Leukemia (2016)

Pediatric acute lymphoblastic leukemia (ALL) is the most common type of malignancy in children with 15% bearing markers for the T-lineage (T-ALL) and 20% of T-ALL patients still suffering disease relapse.Many genes are implicated in T-ALL disease, including Notch, and Notch mutations have been identified in a majority of T-ALL patients. 1Patients with T-ALL relapse with disease usually in the central nervous system (CNS). 2Despite the use of intrathecal therapy and cranial radiation, successful management of CNS disease continues to be problematic in T-ALL. 3Few molecules are known to be associated with T-ALL CNS disease including CCR7, a chemokine receptor normally expressed on naive T cells. 46][7] The involvement of chemokine receptors as well as other molecules regulating cell motility suggests that regulation of T-ALL cell migration is likely to have an important role in T-ALL.Cell signaling molecules that drive normal T-cell proliferation, such as PKCθ, can regulate T-ALL. 8PKCθ activates CARMA1 (also known as CARD11) bringing together Bcl10 and MALT1 leading to NF-κB activation. 9Although higher expression of CARMA1 has been seen in a small subset of T-ALL patients, little is known about how CARMA1 might regulate T-ALL. 10To study the potential role of CARMA1 in T-ALL disease, we used shRNA to knock down CARMA1 expression in the human CEM T-ALL cell line expressing luciferase and GFP (called CARMA1KD), with the level of knockdown ~50% (Supplementary Figure 1A).We transferred the CARMA1KD CEM cells into the immunodeficient NOD.Cg-Prkdc scid Il2rg tm1Wjl /SzJ IL2RG (NSG) mice.Animals receiving CARMA1KD T-ALL cells survived significantly longer than animals receiving parental CEM cells (Figure 1a).We also used a Notch1-ΔE-induced mouse T-ALL model in which hematopoietic precursors from WT C57Bl/6 (called WT/WT Notch1ΔE ; labeled WT) or CARMA1 -/ -(WT/CARMA1 -/ -Notch1ΔE ; labeled CARMA1KO) animals were transduced with Notch1ΔE-GFP and develop T-ALL.Like the xenograft model, we found that WT/CARMA1 -/ -Notch1ΔE (CARMA1KO) animals survived significantly longer than WT/WT Notch1ΔE (WT; Figure 1b).We then asked whether CARMA1 is also involved in human T-ALL disease.Using microarray analyses from patient T-ALL cells, we compared CARMA1 expression in bone marrow (BM) cells from T-ALL patients with BM cells from a non-leukemia control population.CARMA1 expression was significantly higher in the T-ALL patients cells compared with non-leukemic cells (Figure 1c) and other tumor types including lung, liver and breast (Figure 1d).
Heart Failure With Preserved Ejection Fraction
Authors: Kavita Sharma, David A. Kass
Journal: Circulation Research (2014)

The clinical syndrome comprising heart failure (HF) symptoms but with a left ventricular ejection fraction (EF) that is not diminished, eg, HF with preserved EF, is increasingly the predominant form of HF in the developed world, and soon to reach epidemic proportions. It remains among the most challenging of clinical syndromes for the practicing clinician and scientist alike, with a multitude of proposed mechanisms involving the heart and other organs and complex interplay with common comorbidities. Importantly, its morbidity and mortality are on par with HF with reduced EF, and as the list of failed treatments continues to grow, HF with preserved EF clearly represents a major unmet medical need. The field is greatly in need of a more unified approach to its definition and view of the syndrome that engages integrative and reserve pathophysiology beyond that related to the heart alone. We need to reflect on prior treatment failures and the message this is providing, and redirect our approaches likely with a paradigm shift in how the disease is viewed. Success will require interactions between clinicians, translational researchers, and basic physiologists. Here, we review recent translational and clinical research into HF with preserved EF and give perspectives on its evolving demographics and epidemiology, the role of multiorgan deficiencies, potential mechanisms that involve the heart and other organs, clinical trials, and future directions.
Efficacy and safety of sunitinib in patients with metastatic renal cell carcinoma on hemodialysis.
Authors: J. Casper, D. Goebel, V. Gruenwald, A. Flörcken, D. Mueller, K. Toussaint, B. Metzner
Journal: Journal of Clinical Oncology (2011)

4646 Background: Sunitinib treatment is currently a standard of care for the treatment of metastatic renal cell carcinoma. Patients (pts) on hemodialysis however were excluded from studies and only few cases of pts on hemodialysis have been reported. Methods: We have performed a retrospective study by contacting over 100 hemodialysis institutions in Germany. 28 pts have been treated between November 2006 and July 2010. 21 pts, with a median age of 64 years (range 47-82) and a median ECOG of 1 (range 0-2) were evaluable. 16 pts had an intermediate risk, 2 pts a low risk and 3 pts a poor risk according to MKSCC criteria. Sunitinib doses applied were 25 mg (3 pts), 37.5 mg (8 pts) and 50 mg (9 pts) in the 4 week treatment and 2 weeks off schedule. 1 pat received 50 mg continuously. In median 9 courses were given (range 1–18). Results: The estimated median progression free survival of this cohort is 15 months (95% CI 11-19) and the median overall survival 29 months (95% CI 12-47). 1 of 21 pts (5%) reached a complete remission, 10 pts (47%) a partial remission, 5 pts (24%) had stable disease, 3 (14%) had progressive disease and 2 pts. (10%) were not evaluable because of insufficient data. Most side effects were comparable to those commonly reported. However nausea (4 pts, 19%), vomiting (3 pts, 14%), hypertension (4 pts, 19%), and cardiac failure (2 pts, 10%) may have had a higher incidence. In 5 of 10 pts receiving 50 mg sunitinib dose reductions were performed. Therapy was discontinued due to side effects in 7 of 21 pts (4 of 8 with 37.5 mg, 3 of 10 with 50 mg sunitinib) without prior dose reduction. Conclusions: Therapy with sunitinib in pts. on hemodialysis is feasible and well tolerated. Hypertension, nausea and vomiting as well as cardiac failure may be more frequent. Dose adjustments may be necessary more frequently. Despite this response rates as well as progression free and overall survival compare well with pts with normal kidney function.
Two different doses of fulvestrant (F) as second- or further-line hormone therapy (HT) in elderly patients with metastatic breast cancer (MBC).
Authors: Alessandro Comandone, Cristiano Oliva, Antonella Boglione, Orietta Dal Canton, Simona Chiado Cutin, Paolo Pochettino, Ferdinando Garetto, Davide Ottaviani, Maria Luisa Sartori, Elena Giubellino, Paola Bergnolo
Journal: Journal of Clinical Oncology (2014)

e11547 Background: Fulvestrant (F) is a pure antiestrogen drug approved for MBC of postmenopausal women with estrogen receptor positive disease. The CONFIRM trial has recently demonstrated that a double dose (500 mg/monthly) of F is superior to 250 mg/monthly dose as PFS in MBC. In elderly (age >65 years) patients (pts) HT is the preferred choice when disease is hormone sensitive. The aim of our study was to determine the comparative activity, toxicity and feasibility of two different schedule of F in elderly women with MBC. Methods: A retrospective study was carried out in elderly MBC pts treated between 2006-2013 with F after at least one HT. Pts received F 250 or 500 mg im every 28 days until progression. Median age was 70,5 years (66-84). ER e PR status was known in all pts: ER+/PR+ were 56 (94%), ER+/PR- 4 (6%). Histological type were: ductal 52 (86,6%), lobular 8 (13,4%). HER 2 was positive in 4 (6%) pts. All pts were metastatic: 20 (33%) with bone metastasis alone, 40 (66%) with visceral involvement, 22 (36,6%) had both visceral and skeletal metastasis. All pts had been heavily pretreated: 21 with one previous line HT (antiaromatase), 31 with two lines (both antiaromatase followed by tamoxifene or anastrozole followed by examestane). 8 women were at their forth HT line. F was administered for a median of 4 months (3-21). Results: 34 pts (56,6%) experienced clinical benefit defined as SD (28 pts, 46,6%) and PR (6, 10%). Median TTP was 241 days for 250 mg and 276 for 500 mg (p 0.72). Pts with visceral disease had a worse outcome (TTP 208 for visceral ± bone versus 345 for bone alone, p 0.03). The treatment was well tolerated at both doses. Only one patient dropped out for G2 diarrhoea. Conclusions: In elderly pts F is well tolerated both at 500 either 250 mg monthly even in heavily pretreated women. Drug is active even in third and further lines of HT. In our study no difference in efficacy and tolerability was seen despite the different doses.
Endoplasmic Reticulum Stress Protein GRP78 Modulates Lipid Metabolism to Control Drug Sensitivity and Antitumor Immunity in Breast Cancer
Authors: Katherine L. Cook, David R. Soto-Pantoja, Pamela A.G. Clarke, M. Idalia Cruz, Alan Zwart, Anni Wärri, Leena Hilakivi-Clarke, David D. Roberts, Robert Clarke
Journal: Cancer Research (2016)

The unfolded protein response is an endoplasmic reticulum stress pathway mediated by the protein chaperone glucose regulated-protein 78 (GRP78). Metabolic analysis of breast cancer cells shows that GRP78 silencing increases the intracellular concentrations of essential polyunsaturated fats, including linoleic acid. Accumulation of fatty acids is due to an inhibition of mitochondrial fatty acid transport, resulting in a reduction of fatty acid oxidation. These data suggest a novel role of GRP78-mediating cellular metabolism. We validated the effect of GRP78-regulated metabolite changes by treating tumor-bearing mice with tamoxifen and/or linoleic acid. Tumors treated with linoleic acid plus tamoxifen exhibited reduced tumor area and tumor weight. Inhibition of either GRP78 or linoleic acid treatment increased MCP-1 serum levels, decreased CD47 expression, and increased macrophage infiltration, suggesting a novel role for GRP78 in regulating innate immunity. GRP78 control of fatty acid oxidation may represent a new homeostatic function for GRP78. Cancer Res; 76(19); 5657-70. ©2016 AACR.
Pre-eclampsia and childhood asthma
Authors: Maria C. Magnus, Siri E. Håberg, Per Magnus, Anders Engeland, Per Nafstad, Øystein Karlstad, Wenche Nystad
Journal: European Respiratory Journal (2016)

Studies of pre-eclampsia and childhood asthma are conflicting, and none have performed a formal mediation analysis of preterm birth. We examined the association between pre-eclampsia and asthma at 7 years using national registries, including all births in Norway from 1999 to 2006 (n=406 907), and a subsample of children in the Norwegian Mother and Child Cohort Study (MoBa) (n=45 028) using log-linear regression. We performed a mediation analysis of preterm birth, and a sibling comparison to evaluate unobserved confounding. There was a positive association between pre-eclampsia and asthma in the registry study, with an adjusted relative risk of 1.31 (95% CI 1.22–1.41), but not in MoBa, which had an adjusted relative risk of 1.19 (95% CI 0.99–1.44). The odds ratios for the direct effect not mediated through preterm birth and the indirect effect in the registry linkage were 1.19 (95% CI 1.10–1.29) and 1.12 (95% CI 1.11–1.14), respectively. The sibling comparison indicated no association between pre-eclampsia and asthma (adjusted OR 1.07, 95% CI 0.87–1.33). In this large study, which used different datasets and analytic approaches, there was little evidence for an association between pre-eclampsia and childhood asthma. The association was weak and largely explained by pre-term birth and confounders shared by siblings.
Evaluating Patients for Concussion
Authors: Rebecca Voelker
Journal: JAMA (2016)

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EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update
Authors: R Agca, S C Heslinga, S Rollefstad, M Heslinga, I B McInnes, M J L Peters, T K Kvien, M Dougados, H Radner, F Atzeni, J Primdahl, A Södergren, S Wallberg Jonsson, J van Rompay, C Zabalan, T R Pedersen, L Jacobsson, K de Vlam, M A Gonzalez-Gay, A G Semb, G D Kitas, Y M Smulders, Z Szekanecz, N Sattar, D P M Symmons, M T Nurmohamed
Journal: Annals of the Rheumatic Diseases (2016)

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.