tbuckley/cabot-search huggingface dataset:
Abstract 16977: Estimating the Health Workforce Requirements for Hypertension Management in Rural Western Kenya
Authors: Danielle J Lee, Jemima H Kamano, Deborah Tulienge, Peninah Kiptoo, Claire Kofler, Sylvester Kimaiyo, Valentin Fuster, Hari Balasubramanian, Rajesh Vedanthan
Journal: Circulation (2015)

Background: Hypertension is a major risk factor for cardiovascular disease, and the leading risk factor for mortality in sub-Saharan Africa. Yet hypertension treatment and control rates are low. One strategy to address inadequate hypertension treatment in Kenya is task redistribution of care from physicians to nurses. However, the workforce requirements for comprehensive hypertension treatment are not well known. Objective: To develop a needs-based workforce estimation model in order to estimate the health workforce requirements for stable, long-term hypertension management in Kenya. Methods: A mixed-methods approach was used to assess a nurse-based hypertension program in western Kenya. We conducted 7 key informant interviews and 6 focus group discussions among program managers, nurses, community health workers, community leaders, and patients. Qualitative transcripts were analyzed using content analysis with deductive and inductive codes. We also conducted time-motion studies of 118 patient encounters over 7 clinical days in 7 rural health facilities. Finally, we conducted a two-round Delphi exercise, involving anonymous surveys of 8 experts in hypertension and chronic disease care. Results of the time-motion studies and Delphi exercise were summarized using descriptive statistics. The results were inputted into a needs-based health workforce estimation model using Microsoft Excel. Sensitivity analyses were performed, using alternate input values for disease complexity, follow-up interval, and nurse productivity. Results: For a total of 5000 patients, with 60%, 32%, and 8% requiring follow-up visits in 1, 2, and 3 months, respectively, we estimated that 3928 patient encounters are required per month. Our data yielded an estimated clinical capacity of each nurse full-time equivalent (FTE) at 81 patient encounters/month. Thus, 49 nurse FTEs would be required to treat 5000 hypertension patients. Conclusions: A simple needs-based workforce estimation model for hypertension management is able to provide workforce projections that are useful for program planning, human resource allocation, and policy formulation. This approach can serve as a benchmark for future studies to manage chronic diseases in low- and middle-income countries.
Re-evaluation of a 2014 multi-country European outbreak of Salmonella Enteritidis phage type 14b using recent epidemiological and molecular data
Authors: Stefan Hörmansdorfer, Ute Messelhäußer, Albert Rampp, Katharina Schönberger, Tim Dallman, Franz Allerberger, Christian Kornschober, Andreas Sing, Peter Wallner, Andreas Zapf
Journal: Eurosurveillance (2017)

A European multi-country outbreak of Salmonella Enteritidis phage type (PT) 14b occurred from March to November 2014 associated with the consumption of eggs. The outbreak involved more than 400 human cases from France, Luxembourg, Austria and the United Kingdom. In 2016–2017, it has been re-evaluated combining recent epidemiological results with latest molecular data. The outbreak was traced back to one large Bavarian egg producer with four distinct premises, three located in Bavaria, one in the Czech Republic. The outbreak isolates of S. Enteritidis PT 14b were grouped into three closely related clades by whole genome sequencing. Two of these clades could be referred to two Bavarian premises of the egg producer on the basis of epidemiological and molecular data, while epidemiological data presumably linked the third clade to another premises of the egg producer. Interestingly and in contrast to the situation in other European countries where several outbreaks were documented, all notified 91 laboratory-confirmed cases of S. Enteritidis PT 14b from Bavaria were sporadic, singular cases not belonging to any epidemiological outbreaks. In conclusion, as demonstrated here, the resolution of food-related outbreaks with such a high discriminatory power is rare in outbreak investigation.
White Matter Plasticity in the Adult Brain
Authors: Cassandra Sampaio-Baptista, Heidi Johansen-Berg
Journal: Neuron (2017)

The study of brain plasticity has tended to focus on the synapse, where well-described activity-dependent mechanisms are known to play a key role in learning and memory. However, it is becoming increasingly clear that plasticity occurs beyond the synapse. This review focuses on the emerging concept of white matter plasticity. For example, there is growing evidence, both from animal studies and from human neuroimaging, that activity-dependent regulation of myelin may play a role in learning. This previously overlooked phenomenon may provide a complementary but powerful route through which experience shapes the brain.
Abstract #4723: MicroRNA-221/222 confer breast cancer resistance to fulvestrant by targeting multiple oncogenic activities
Authors: Xi Rao, Gianpiero Di Leva, Meng Li, Fang Fang, Curtis Balch, John Thomson, Scott Hammond, Corinna Hartman-Frey, Yunlong Liu, Carlo Croce, Kenneth Nephew
Journal: Cancer Research (2009)

Breast cancer is the leading cause of female death worldwide and will afflict 1 of 8 U.S. women in their lifetime. One commonly used breast cancer therapy, fulvestrant, has potent activity against hormone-sensitive breast cancers. However, almost all patients eventually develop resistance to fulvestrant, and the underlying mechanism(s) of loss of drug response remains unknown. We had previously generated a fulvestrant-resistant cell line (MCF7-F) highly characteristic of this clinical phenomenon (Cancer Res, 66, 2006). MicroRNAs, 19-22-nucleotide non-coding regulatory RNAs, have recently been implicated in breast cancer, and we subjected MCF7-F cells to microRNA expression analysis using a 612-feature custom microarray. From those analyses, we determined that two specific microRNAs, miR-221 and miR-222, were significantly upregulated by 9-fold and 6-fold respectively in MCF7-F cells (as compared to the parental MCF7 cell line). To further assess the role of miR-221/222 in MCF7-F cells, we downregulated miR-221/222 by using chemically stable, antisense oligoribonucleotides (\#8220;antagomirs\#8221;) against those specific microRNA sequences, demonstrating that miR-221/222 antagomir treatment significantly decreased cell proliferation by 40%. In addition, the cyclin-dependent kinase inhibitor (and tumor suppressor) p27(Kip1) (CDKN1B, a known target protein for miR-221/222), which is downregulated in MCF7-F, was upregulated after antagomir treatment, with cell cycle analyses demonstrating G1 cell cycle arrest. Based on this evidence, we hypothesize that miR-221/222 upregulation contributes to the development of fulvestrant resistance, leading to loss of p27(Kip1), which subsequently facilitates estrogen-independent cell cycle progression. However, as any single microRNA likely targets numerous genes to influence the overall malignant phenotype, we sought to identify additional miR-221/222 targets in MCF7-F cells. MCF7-F cells were treated with miR-221/222 antagomirs, and then subjected to Affymetrix gene expression profiling and pathway enrichment analysis. Several well known signaling pathways appeared to be regulated by miR-221/222, including p53, TGF-beta, Notch and MAPK. We are currently validating the regulatory role of miR-221/222 in these pathways and investigating their role in the development of fulvestrant resistance. Overall, the findings indicate that miR-221 and miR-222 may represent promising therapeutic targets for fulvestrant resensitization in patients with advanced breast cancer.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4723.
Abstract 40: Neighborhood Grocery Store Density is Associated with Daily Self-efficacy Among Individuals Enrolled in a Behavioral Weight Loss Intervention Study
Authors: Dara D Mendez, Stephen L Rathbun, Qianheng Ma, Rachel W Goode, Yaguang Zheng, Meghan Mattos, Chris C Imes, Cynthia A Danford, Susan M Sereika, Lu Hu, Lora E Burke
Journal: Circulation (2016)

Introduction: Neighborhood factors may play an important role in the treatment of obesity. However, it is unclear if exposures to certain neighborhood factors influence self-efficacy among individuals attempting to lose weight. Hypothesis: We hypothesized that individuals living in obesogenic neighborhood environments at baseline would have low self-efficacy for resisting urges to eat beyond their recommended eating plan in a 12-mo weight loss study. Methods: We used ecological momentary assessment (EMA) to collect daily data on self-efficacy with an EMA question: How CONFIDENT are you that, if you have an urge to go off your healthy lifestyle plan, you can resist the urge? (value 1 to 10) This EMA question was delivered randomly an average of 5 times/day on a smartphone. Residential address at baseline was geocoded using ArcGIS software and key neighborhood measures (e.g., grocery store and restaurant density, proportion of Black and low income residents, index of neighborhood socioeconomic disadvantage (NSED)) were linked at the census tract level. Data were analyzed using descriptive statistics and linear mixed modeling. Results: The sample (N=136) was predominately female (90%), White (80%), mean (SD) age 51.3 (10.3) years, and mean BMI 34.1 (4.6) kg/m 2 . The residential neighborhoods of participants were predominantly White, middle to high education level, and low poverty. The mean confidence score decreased from 7.3 at month 1 to 6.8 at month 12 (p &lt;.001). A higher level of baseline neighborhood grocery store density was associated with a higher confidence score ( p = .037) (see table). No other neighborhood factor was associated with confidence score. Conclusion: Neighborhood factors, specifically access to grocery stores, may affect an individuals’ ability to lose or maintain weight loss by supporting one’s confidence to maintain a healthy lifestyle. This study needs to be replicated in a larger cohort with a more diverse neighborhood representation.
Mediastinal staging by videomediastinoscopy in clinical N1 non-small cell lung cancer: a prospective multicentre study
Authors: Herbert Decaluwé, Christophe Dooms, Xavier Benoit D'Journo, Sergi Call, David Sanchez, Benedikt Haager, Roel Beelen, Volkan Kara, Thomas Klikovits, Clemens Aigner, Kurt Tournoy, Mahmood Zahin, Johnny Moons, Geoffrey Brioude, Juan Carlos Trujillo, Walter Klepetko, Akif Turna, Bernward Passlick, Laureano Molins, Ramon Rami-Porta, Pascal Thomas, Paul De Leyn
Journal: European Respiratory Journal (2017)

A quarter of patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on positron emission tomography–computed tomography (PET-CT) imaging have occult mediastinal nodal involvement (N2 disease). In a prospective study, endosonography alone had an unsatisfactory sensitivity (38%) in detecting N2 disease. The current prospective multicentre trial investigated the sensitivity of preoperative mediastinal staging by video-assisted mediastinoscopy (VAM) or VAM-lymphadenectomy (VAMLA). Consecutive patients with operable and resectable (suspected) NSCLC and cN1 after PET-CT imaging underwent VAM(LA). The primary study outcome was sensitivity to detect N2 disease. Secondary endpoints were the prevalence of N2 disease, negative predictive value (NPV) and accuracy of VAM(LA). Out of 105 patients with cN1 on imaging, 26% eventually developed N2 disease. Invasive mediastinal staging with VAM(LA) had a sensitivity of 73% to detect N2 disease. The NPV was 92% and accuracy 93%. Median number of assessed lymph node stations during VAM(LA) was 4 (IQR 3–5), and in 96%, at least three stations were assessed. VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1 lung cancer, and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with a one in four chance of occult-positive mediastinal nodes after negative PET-CT.
After PCI in AF, dual antithrombotic therapy with dabigatran reduced bleeding compared with triple therapy
Authors: Dominic L. Raco
Journal: Annals of Internal Medicine (2017)

Source Citation Cannon CP, Bhatt DL, Oldgren J, et al; RE-DUAL PCI Steering Committee and Investigators. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. 2017;377:1513-24. 28844193
Simvastatin with or without ezetimibe in familial hypercholesterolemia (vol 358, pg 1431, 2008)
Authors: J. J. P. Kastelein, F. Akdim, E. S. G. Stroes, A. H. Zwinderman, M. L. Bots, A. F. H. Stalenhoef, F. L. J. Visseren, E. J. G. Sijbrands, M. D. Trip, E. A. Stein, D. Gaudet, R. Duivenvoorden, E. P. Veltri, A. D. Marais, E. de Groot
Journal: New England Journal of Medicine (2008)
Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health
Authors: Jun Zou, Benoit Chassaing, Vishal Singh, Michael Pellizzon, Matthew Ricci, Michael D. Fythe, Matam Vijay Kumar, Andrew T. Gewirtz
Journal: Cell Host & Microbe (2017)
Myelofibrosis‐Related Anemia
Authors: Leonard Naymagon, John Mascarenhas
Journal: HemaSphere (2017)

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder characterized by pathological myeloproliferation and aberrant cytokine production resulting in progressive fibrosis, inflammation, and functional compromise of the bone marrow niche. Patients with MF develop splenomegaly (due to extramedullary hematopoiesis), hypercatabolic symptoms (due to overexpression of inflammatory cytokines), and anemia (due to bone marrow failure and splenic sequestration). MF remains curable only with allogeneic hematopoietic stem cell transplantation (ASCT), a therapy that few MF patients are deemed fit to undergo. The goals of treatment are thus often palliative. The approval of the JAK inhibitor ruxolitinib has done much to address the burden of splenomegaly and constitutional symptoms of patients with MF; however, therapy-related anemia is often an anticipated downside. Anemia thus remains a challenge in the management of MF and represents a major unmet need. Intractable anemia depresses quality of life, portends poor outcomes, and can act to restrict access to palliative JAK inhibition in some patients. While therapies for MF-related anemia do exist, they are limited in their efficacy, durability, and tolerability. Therapies currently in development promise improved anemia-specific outcomes; however, are still early in the pathway to regulatory approval and regular clinical use. In this review, we will discuss established and emerging treatments for MF-related anemia. We will give particular attention to developmental therapies which herald significant progress in the understanding and management of MF-related anemia.
Dynamic Adaptation of Tumor Immune Response With Nivolumab Demonstrated by 18F-FDG PET/CT
Authors: Naghmehossadat Eshghi, Tamara F. Lundeen, Phillip H. Kuo
Journal: Clinical Nuclear Medicine (2017)

Abstract A 61-year-old woman with lung adenocarcinoma failed first-line treatment and was placed on immunotherapy with nivolumab. FDG-PET/CT before immunotherapy showed metastases to thoracic nodes, liver, adrenal gland, and skeleton. Seven weeks after starting nivolumab, FDG-PET/CT showed mild residual activity in thoracic nodes and otherwise complete response. After 15 weeks, enlarged and FDG-avid axillary lymphadenopathy and worsening supraclavicular lymphadenopathy developed. After 20 weeks, FDG-PET/CT demonstrated marked improvement of axillary and supraclavicular lymphadenopathy. This case demonstrates that later progression of disease can still respond to continuing immunotherapy, hypothetically because of dynamic adaptations in the tug-of-war between the immunotherapy-augmented immune system and tumor.
ConsensusDriver Improves upon Individual Algorithms for Predicting Driver Alterations in Different Cancer Types and Individual Patients
Authors: Denis Bertrand, Sibyl Drissler, Burton K. Chia, Jia Yu Koh, Chenhao Li, Chayaporn Suphavilai, Iain Beehuat Tan, Niranjan Nagarajan
Journal: Cancer Research (2017)

Abstract Existing cancer driver prediction methods are based on very different assumptions and each of them can detect only a particular subset of driver genes. Here we perform a comprehensive assessment of 18 driver prediction methods on more than 3,400 tumor samples from 15 cancer types, all to determine their suitability in guiding precision medicine efforts. We categorized these methods into five groups: functional impact on proteins in general (FI) or specific to cancer (FIC), cohort-based analysis for recurrent mutations (CBA), mutations with expression correlation (MEC), and methods that use gene interaction network-based analysis (INA). The performance of driver prediction methods varied considerably, with concordance with a gold standard varying from 9% to 68%. FI methods showed relatively poor performance (concordance &amp;lt;22%), while CBA methods provided conservative results but required large sample sizes for high sensitivity. INA methods, through the integration of genomic and transcriptomic data, and FIC methods, by training cancer-specific models, provided the best trade-off between sensitivity and specificity. As the methods were found to predict different subsets of driver genes, we propose a novel consensus-based approach, ConsensusDriver, which significantly improves the quality of predictions (20% increase in sensitivity) in patient subgroups or even individual patients. Consensus-based methods like ConsensusDriver promise to harness the strengths of different driver prediction paradigms. Significance: These findings assess state-of-the-art cancer driver prediction methods and develop a new and improved consensus-based approach for use in precision oncology. Cancer Res; 78(1); 290–301. ©2017 AACR.
Familial pneumothorax: towards precision medicine
Authors: Rachel M Scott, Elizabeth P Henske, Benjamin Raby, Philip M Boone, Rosemary A Rusk, Stefan J Marciniak
Journal: Thorax (2017)

One in 10 patients suffering from primary spontaneous pneumothoraces has a family history of the disorder. Such familial pneumothoraces can occur in isolation, but can also be the presentation of serious genetic disorders with life-threatening vascular or cancerous complications. As the pneumothorax frequently precedes the more dangerous complications by many years, it provides an opportunity to intervene in a focused manner, permitting the practice of precision medicine. In this review, we will discuss the clinical manifestations and underlying biology of the genetic causes of familial pneumothorax.
Efficacy and safety of lenvatinib for the treatment of patients with<sup> 131</sup>I-refractory differentiated thyroid cancer with and without prior VEGF-targeted therapy.
Authors: Kate Newbold, Rossella Elisei, Matthew Hiram Taylor, Monika K. Krzyzanowska, Manisha H. Shah, Ana O. Hoff, Bruce Robinson, Corina Dutcus, James Song, Mouhammed Amir Habra
Journal: Journal of Clinical Oncology (2015)

6013 Background: Lenvatinib (LEN), an oral multikinase inhibitor of VEGFR1–3, FGFR1–4, PDGFRα, RET, and KIT, significantly prolonged progression-free survival (PFS) vs placebo in the phase 3 SELECT trial of patients (pts) with 131I-refractory differentiated thyroid cancer (RR-DTC). Here we report the prespecified analysis of LEN-treated pts based on prior VEGF-targeted therapy exposure. Methods: Pts with measurable RR-DTC and independent radiologic documentation of disease progression within 13 months were randomized 2:1 to LEN (24 mg/d; 28-d cycle) or placebo. Pts were stratified by age, region, and prior VEGF-targeted therapy (0 [VEGF-naive] or 1 [prior-VEGF]). Results: 195/261 (75%) LEN-treated and 104/131 (79%) placebo-treated pts were naive to VEGF-targeted therapy. 93 Pts had received prior-VEGF therapy: sorafenib, 77%; sunitinib, 9%; pazopanib, 5%; other, 9%. LEN prolonged PFS vs placebo in both groups (Table; VEGF-naive: HR 0.20; 95% CI 0.14–0.27; P<0.0001; prior-VEGF: HR 0.22; 95% CI 0.12–0.41; P<0.0001). Objective response rates (ORR) were similar between both groups (Table). VEGF-naive pts received more cycles of LEN than prior-VEGF pts (medians of 16 and 12.5 cycles, respectively), but had lower overall daily dose intensity (16.1 and 20.1 mg/d, respectively). The proportion of LEN-treated pts with at least 1 dose reduction was similar (VEGF naive: 87%; prior-VEGF: 82%), but VEGF-naive pts had an earlier median time to first dose reduction than pts with prior-VEGF (8.9 and 14.8 weeks, respectively). Most common LEN-emergent adverse events for VEGF-naive and prior-VEGF pts were, respectively: hypertension (72% and 62%), diarrhea (70% and 61%), decreased appetite (54% and 55%), decreased weight (52% and 49%), and nausea (45% and 52%). Conclusions: In SELECT, LEN conferred comparable efficacy in pts with and without prior exposure to VEGF-targeted therapy, with similar safety profiles. Clinical trial information: NCT01321554. Lenvatinib Placebo VEGF-naive n=195 Prior-VEGF n=66 VEGF-naive n=104 Prior-VEGF n=27 Median PFS, months (95% CI) 18.7 (16.4–NE) 15.1 (8.8–NE) 3.6 (2.1–5.3) 3.6 (1.9–3.7) ORR, n (%) 128 (65.6) 41 (62.1) 1 (1.0) 1 (3.7) NE, not evaluable.
Abstract 19436: Outcomes of Reoperation After Acute Type A Aortic Dissection: Implications for Index Repair Strategy
Authors: Hanghang Wang, Ehsan Benrashid, Jeffrey Keenan, David Ranney, Babatunde Yerokun, Alice Wang, Jeffrey Gaca, G. Chad Hughes
Journal: Circulation (2016)

Introduction:  The optimal surgical approach for management of acute Type A aortic dissection remains controversial. Arguments in favor of limited index repair include higher operative risk associated with more extensive (e.g. total arch) repair, while arguments in favor of extended repair include concerns regarding outcomes of reoperation. This study aimed to assess outcomes of reoperation after acute Type A dissection repair to guide decision-making around initial operative strategy.   Methods:  All patients (n = 90) who underwent reoperation (n = 127 procedures) at a single referral institution from 08/2005 to 04/2016 after prior acute Type A dissection repair were reviewed. The primary outcome was 30-day/in-hospital mortality. Secondary outcomes included organ-specific morbidity, and one and five-year outcomes as estimated using Kaplan-Meier method.   Results:  The median interval between index Type A repair and first reoperation was 5 years. The majority of reoperations were proximal aortic (aortic valve, aortic root, or ascending) or aortic arch procedures (67%, n = 85, Table); most reoperations were performed in the elective setting (85%, n = 108). Thirty-day mortality was 7.9% (elective: 6.5%, non-elective: 16%) with low rates of organ-specific morbidity. Additional non-staged reoperations were required in 19 patients after the first reoperation, the vast majority (15/19; 79%) of which were distal aortic procedures, during a median follow-up of 2.5 years. One- and five-year survival after initial reoperation was 80% and 62%, respectively.   Conclusions:  Reoperation after acute Type A aortic dissection repair in the elective setting is associated with low rates of mortality and morbidity. Long-term survival was acceptable and the incidence of needing additional procedures was low. These data support use of a more limited index repair for acute Type A dissection as elective reoperations, if needed, can be performed safely in referral aortic centers.