bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repositioning FDA-Approved Drugs in Combination with Epigenetic Drugs to Reprogram Colon Cancer Epigenome
Authors: Raynal Noël J.-M. , Da Costa Elodie M. , Lee Justin T. , Gharibyan Vazganush , Ahmed Saira , Zhang Hanghang , Sato Takahiro , Malouf Gabriel G. , Issa Jean-Pierre J. 
Published: December 2016

Abstract
Epigenetic drugs, such as DNA methylation inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi), are approved in monotherapy for cancer treatment. These drugs reprogram gene expression profiles, reactivate tumor suppressor genes (TSG) producing cancer cell differentiation and apoptosis. Epigenetic drugs have been shown to synergize with other epigenetic drugs or various anticancer drugs. To discover new molecular entities that enhance epigenetic therapy, we performed a high-throughput screening using FDA-approved libraries in combination with DNMTi or HDACi. As a screening model, we used YB5 system, a human colon cancer cell line, which contains an epigenetically silenced CMV-GFP locus, mimicking TSG silencing in cancer. CMV-GFP reactivation is triggered by DNMTi or HDACi and responds synergistically to DNMTi/HDACi combination, which phenocopies TSG reactivation upon epigenetic therapy. GFP fluorescence was used as a quantitative readout for epigenetic activity. We discovered that 45 FDA-approved drugs (4% of all drugs tested) in our FDA-approved libraries enhanced DNMTi and HDACi activity, mainly belonging to anticancer and antiarrhythmic drug classes. Transcriptome analysis revealed that combination of decitabine (DNMTi) with the antiarrhythmic proscillaridin A produced profound gene expression reprogramming, which was associated with downregulation of 153 epigenetic regulators, including two known oncogenes in colon cancer (SYMD3 and KDM8). Also, we identified about 85 FDA-approved drugs that antagonized DNMTi and HDACi activity through cytotoxic mechanisms, suggesting detrimental drug interactions for patients undergoing epigenetic therapy. Overall, our drug screening identified new combinations of epigenetic and FDA-approved drugs, which can be rapidly implemented into clinical trials. Mol Cancer Ther; 16(2); 397–407. ©2016 AACR.
Venous Thrombotic Recurrence After Cerebral Venous Thrombosis
Authors: Palazzo Paola , Agius Pierre , Ingrand Pierre , Ciron Jonathan , Lamy Matthias , Berthomet Aline , Cantagrel Paul , Neau Jean-Philippe 
Published: December 2016

Background and Purpose—
After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence.

Methods—
Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation.

Results—

One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1–247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8;
P
=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2;
P
=0.039), and unknown CVT causes (hazard ratio, 2.81;
P
=0.024) were independently associated with recurrence.

Conclusions—
In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.
Charles Brockden Brown and the Conundrum of Complicity
Authors: Zimmerman David 
Published: December 2016

AbstractCharles Brockden Brown’s four major novels, all written between 1798 and 1800, are devoted to the conundrum of moral complicity—the impossibility of pinpointing moral accountability for harms in a world where intersubjective life makes it impossible to separate one person’s action from the actions of others. This essay argues that for Brown, this conundrum constituted the narrative precondition of fictional storytelling and served as the source of his fiction’s formal innovation, theoretical self-consciousness, and gothic weirdness. This essay suggests, too, that the conundrum of complicity served as the prompt for a synoptic mode of reading that Brown introduced to American fiction.
Uncle Tom across the Sea (and Back): Pierre Faubert and the Haitian Response to Harriet Beecher Stowe
Authors: Albanese Mary Grace 
Published: December 2016

Abstract
The transnational material network of Harriet Beecher Stowe’s Uncle Tom’s Cabin (1852) has enjoyed substantial critical analysis: however, most scholarship tends to focus on the novel’s influence in Europe. Haiti plays a much greater role in the novel than any European country, yet in contrast to Britain, France, or Hungary, the first black republic is seldom considered a serious actor within Uncle Tom’s reception history. This essay considers how Stowe’s cautionary specter of the “San Domingo hour” was translated to Haiti and, in turn, the diverse ways in which Haitians responded to l’Oncle Tom. Ultimately, this essay argues that Haiti, far from being an isolated figure, was aware of, responded to, and cannily attempted to retranslate its own image both at home and abroad. This essay contributes to a long-neglected archive of Haitian cultural production while more broadly asking how Haitian writers revised Stowe’s conceptualization of nationhood.
Use of cidofovir in pediatric patients with adenovirus infection
Authors: Ganapathi Lakshmi , Arnold Alana , Jones Sarah , Patterson Al , Graham Dionne , Harper Marvin , Levy Ofer 
Published: December 2016

Background: Adenoviruses contribute to morbidity and mortality among immunocompromised pediatric patients including stem cell and solid organ transplant recipients. Cidofovir (CDV), an antiviral compound approved by the FDA in 1996, is used for treatment of adenoviral (ADV) infections in immunocompromised patients despite concern of potential nephrotoxicity. Methods: We conducted a retrospective 5-year review at Boston Children’s Hospital of 16 patients (mean age = 6.5 years) receiving 19 courses of CDV. During therapy all pertinent data elements were reviewed to characterize potential response to therapy and incidence of renal dysfunction. Results:Of the 19 CDV courses prescribed, 16 courses (84%) were in patients who had a positive blood ADV Polymerase chain reaction (PCR) alone or in combination with positive ADV PCR/ Direct Immunofluorescence Assay (DFA) at another site. Respiratory symptoms with or without pneumonia were the most common presentation (10/19, 53%). In the majority of blood positive courses (10/16, 63%), viral clearance was also accompanied by clinical response. This was not the case in four courses where patients expired despite viral clearance, including one in which death was directly attributable to adenovirus. There was reversible renal dysfunction observed during the use of CDV.Conclusions: CDV appeared safe and reasonably tolerated for treatment of ADV in this pediatric population and was associated with viral response and clinical improvement in the majority of patients but reversible renal dysfunction was a side effect. Further studies of the efficacy of CDV for immunocompromised children with ADV infection are warranted.
Preliminary results on the control of Aedes spp. in a remote Guatemalan community vulnerable to dengue, chikungunya and Zika virus: community participation and use of low-cost ecological ovillantas for mosquito control
Authors: Ulibarri Gerard , Betanzos Angel , Betanzos Mireya , Rojas Juan Jacobo 
Published: December 2016

Objective: To study the effectiveness of an integrated intervention of health worker training, a low-cost ecological mosquito ovitrap, and community engagement on Aedes spp. mosquito control over 10 months in 2015 in an urban remote community in Guatemala at risk of dengue, chikungunya and Zika virus transmission. Methods: We implemented a three-component integrated intervention consisting of: web-based training of local health personnel in vector control, cluster-randomized assignment of an ecological modified ovitrap (ovillantas: ovi=egg, llanta=tire) or standard ovitraps to capture Aedes spp. mosquito eggs (no efforts have been taken to determine the exact Aedes species at this moment), and community engagement to promote participation of community members and health personnel in the understanding and maintenance of ovitraps for mosquito control. The intervention was implemented in local collaboration with Guatemala’s Ministry of Health’s Vector Control Programme, and in international collaboration with the National Institute of Public Health in Mexico. Findings: Eighty percent of the 25 local health personnel enrolled in the training programme received accreditation of their improved knowledge of vector control. When ovillantas were used in a cluster of ovitraps (several in proximity), significantly more eggs were trapped by ecological ovillantas than standard ovitraps over the 10 month (42 week) study period (t=5.2577; p<0.05). Repetitive filtering and recycling of the attractant solution (or water) kept the ovillanta clean, free from algae growth. Among both community members and health workers, the levels of knowledge, interest, and participation in community mosquito control and trapping increased. Recommendations for enhancing and sustaining community mosquito control were identified. Conclusion: Our three-component integrated intervention proved beneficial to this remote community at risk of mosquito-borne diseases such as dengue, chikungunya, and Zika. The combination of training of health workers, cluster use of low-cost ecological ovillanta to destroy the second generation of mosquitoes, and community engagement ensured the project met local needs and fostered collaboration and participation of the community, which can help improve sustainability. The ovillanta intervention and methodology may be modified to target other species such as Culex, should it be established that such mosquitoes carry Zika virus in addition to Aedes.
Laboratory Evidence on the Effects of Sponsorship on the Competitive Preferences of Men and Women
Authors: Baldiga Nancy R. , Coffman Katherine B. 
Published: December 2016

Sponsorship programs have been proposed as one way to promote female advancement in competitive career fields. A sponsor is someone who advocates for a protégé, and in doing so, takes a stake in her success. We use a laboratory experiment to explore two channels through which sponsorship has been posited to increase advancement in a competitive workplace. In our setting, being sponsored provides a vote of confidence and/or creates a link between the protégé’s and sponsor’s payoffs. We find that both features of sponsorship significantly increase willingness to compete among men on average, while neither of these channels significantly increases willingness to compete among women on average. As a result, sponsorship does not close the gender gap in competitiveness or earnings. We discuss how these insights from the laboratory could help to inform the design of sponsorship programs in the field. Data, as supplemental material, are available at https://doi.org/10.1287/mnsc.2016.2606 . This paper was accepted by Uri Gneezy, behavioral economics.
0/1 Polytopes with Quadratic Chvátal Rank
Authors: Rothvoß Thomas , Sanità Laura 
Published: December 2016

For a polytope P, the Chvátal closure P′ ⊆ P is obtained by simultaneously strengthening all feasible inequalities cx ⩽ β (with integral c) to cx ⩽ ⌊β⌋. The number of iterations of this procedure that are needed until the integral hull of P is reached is called the Chvátal rank. If P ⊆ [0, 1]n, then it is known that O(n2 log n) iterations always suffice and at least (1 + 1/e − o(1))n iterations are sometimes needed, leaving a huge gap between lower and upper bounds. We prove that there is a polytope contained in the 0/1 cube that has Chvátal rank Ω(n2), closing the gap up to a logarithmic factor. In fact, even a superlinear lower bound was mentioned as an open problem by several authors. Our choice of P is the convex hull of a semi-random Knapsack polytope and a single fractional vertex. The main technical ingredient is linking the Chvátal rank to simultaneous Diophantine approximations w.r.t. the ‖·‖1-norm of the normal vector defining P.
Design of the New York City Macroscope: Innovations in Population Health
Surveillance Using Electronic Health Records
Authors: Newton-Dame Remle , McVeigh Katharine H. , Schreibstein Lauren , Perlman Sharon , Lurie-Moroni Liz , Jacobson Laura , Greene Carolyn , Snell Elisabeth , Thorpe Lorna E. 
Published: December 2016

Introduction: Electronic health records (EHRs) have the potential to offer
real-time, inexpensive standardized health data about chronic health conditions. Despite
rapid expansion, EHR data evaluations for chronic disease surveillance have been
limited. We present design and methods for the New York City (NYC) Macroscope, an
EHR-based chronic disease surveillance system.This methods report is the first in a
three part series describing the development and validation of the NYC Macroscope. This
report describes in detail the infrastructure underlying the NYC Macroscope; indicator
definitions; design decisions that were made to maximize data quality; characteristics
of the population sampled; completeness of data collected; and lessons learned from
doing this work. The second report describes the methods used to evaluate the validity
and robustness of NYC Macroscope prevalence estimates; presents validation results for
estimates of obesity, smoking, depression and influenza vaccination; and discusses the
implications of our findings for NYC and for other jurisdictions embarking on similar
work. The third report applies the same validation methods to metabolic outcomes,
including the prevalence, treatment and control of diabetes, hypertension and
hyperlipidemia.Methods: We designed the NYC Macroscope for comparison to a local “gold
standard,” the 2013-14 NYC Health and Nutrition Examination Survey, and the telephonic
2013 Community Health Survey. NYC Macroscope indicators covered prevalence, treatment,
and control of diabetes, hypertension, and hyperlipidemia; and prevalence of influenza
vaccination, obesity, depression and smoking. Indicators were stratified by age, sex,
and neighborhood poverty, and weighted to the in-care NYC population and limited to
primary care patients. Indicator queries were distributed to a virtual network of
primary care practices; 392 practices and 716,076 adult patients were retained in the
final sample.Findings: The NYC Macroscope covered 10% of primary care providers and 15%
of all adult patients in NYC in 2013 (8-47% of patients by neighborhood). Data
completeness varied by domain from 98% for blood pressure among patients with
hypertension to 33% for depression screening.Discussion: Design and validation efforts
undertaken by NYC are described here to provide one potential blueprint for leveraging
EHRs for population health monitoring. To replicate a model like NYC Macroscope,
jurisdictions should establish buy-in; build informatics capacity; use standard, simple
case definitions; establish documentation quality thresholds; restrict to primary care
providers; and weight the sample to a target population.
Bilateral Lower-Extremity Edema Caused by Iliopsoas Bursal Distention after Hip Arthroplasty
Authors: Avasarala Sameer K. , Ahsan Syed T. 
Published: December 2016

Lower-extremity edema is encountered by internists, nephrologists, vascular specialists, and many others. We report a case of an elderly woman who presented with a painful, swollen left leg. Without a clear diagnosis, she had been taking diuretics for the past 8 years for swelling in both legs. After extensive investigation, we found that her lower-extremity edema was due to bilateral iliopsoas bursal distention secondary to degeneration of her hip prostheses. Chronic breakdown of the polyethylene component of the hip prostheses had led to a communication between the artificial joints and the iliopsoas bursae. With the aid of ultrasonographic guidance, she underwent drainage, followed by clinical and radiographic improvement.
Although case reports have described leg swelling arising from extravascular compression by enlarged iliopsoas bursae, we think that this is the first case of clinically significant bilateral lower-extremity edema arising from that cause. More important than the novelty is the inappropriate use of diuretics to treat lower-extremity edema without first establishing a diagnosis.
Figure-Ground Organization in Visual Cortex for Natural Scenes
Authors: Williford Jonathan R. , von der Heydt Rüdiger 
Published: December 2016

AbstractFigure-ground organization and border-ownership assignment are essential for understanding natural scenes. It has been shown that many neurons in the macaque visual cortex signal border-ownership in displays of simple geometric shapes such as squares, but how well these neurons resolve border-ownership in natural scenes is not known. We studied area V2 neurons in behaving macaques with static images of complex natural scenes. We found that about half of the neurons were border-ownership selective for contours in natural scenes, and this selectivity originated from the image context. The border-ownership signals emerged within 70 ms after stimulus onset, only ∼30 ms after response onset. A substantial fraction of neurons were highly consistent across scenes. Thus, the cortical mechanisms of figure-ground organization are fast and efficient even in images of complex natural scenes. Understanding how the brain performs this task so fast remains a challenge.
Language in Context: MEG Evidence for Modality-General and -Specific Responses to Reference Resolution
Authors: Brodbeck Christian , Gwilliams Laura , Pylkkänen Liina 
Published: December 2016

AbstractSuccessful language comprehension critically depends on our ability to link linguistic expressions to the entities they refer to. Without reference resolution, newly encountered language cannot be related to previously acquired knowledge. The human experience includes many different types of referents, some visual, some auditory, some very abstract. Does the neural basis of reference resolution depend on the nature of the referents, or do our brains use a modality-general mechanism for linking meanings to referents? Here we report evidence for both. Using magnetoencephalography (MEG), we varied both the modality of referents, which consisted either of visual or auditory objects, and the point at which reference resolution was possible within sentences. Source-localized MEG responses revealed brain activity associated with reference resolution that was independent of the modality of the referents, localized to the medial parietal lobe and starting ∼415 ms after the onset of reference resolving words. A modality-specific response to reference resolution in auditory domains was also found, in the vicinity of auditory cortex. Our results suggest that referential language processing cannot be reduced to processing in classical language regions and representations of the referential domain in modality-specific neural systems. Instead, our results suggest that reference resolution engages medial parietal cortex, which supports a mechanism for referential processing regardless of the content modality.
The Caudate Nucleus Mediates Learning of Stimulus–Control State Associations
Authors: Chiu Yu-Chin , Jiang Jiefeng , Egner Tobias 
Published: December 2016

A longstanding dichotomy in cognitive psychology and neuroscience pits controlled, top-down driven behavior against associative, bottom-up driven behavior, where cognitive control processes allow us to override well-learned stimulus–response (S–R) associations. By contrast, some previous studies have raised the intriguing possibility of an integration between associative and controlled processing in the form of stimulus–control state (S–C) associations, the learned linkage of specific stimuli to particular control states, such as high attentional selectivity. The neural machinery mediating S–C learning remains poorly understood, however. Here, we combined human functional magnetic resonance imaging (fMRI) with a previously developed Stroop protocol that allowed us to dissociate reductions in Stroop interference based on S–R learning from those based on S–C learning. We modeled subjects' acquisition of S–C and S–R associations using an associative learning model and then used trial-by-trial S–C and S–R prediction error (PE) estimates in model-based behavioral and fMRI analyses. We found that PE estimates derived from S–C and S–R associations accounted for the reductions in behavioral Stroop interference effects in the S–C and S–R learning conditions, respectively. Moreover, model-based fMRI analyses identified the caudate nucleus as the key structure involved in selectively updating stimulus–control state associations. Complementary analyses also revealed a greater reliance on parietal cortex when using the learned S–R versus S–C associations to minimize Stroop interference. These results support the emerging view that generalizable control states can become associated with specific bottom-up cues, and they place the caudate nucleus of the dorsal striatum at the center of the neural stimulus–control learning machinery.SIGNIFICANCE STATEMENTPrevious behavioral studies have demonstrated that control states, for instance, heightened attentional selectivity, can become directly associated with, and subsequently retrieved by, particular stimuli, thus breaking down the traditional dichotomy between top-down and bottom-up driven behavior. However, the neural mechanisms underlying this type of stimulus–control learning remain poorly understood. We therefore combined noninvasive human neuroimaging with a task that allowed us to dissociate the acquisition of stimulus–control associations from that of stimulus–response associations. The results revealed the caudate nucleus as the key brain structure involved in selectively driving stimulus–control learning. These data represent the first identification of the neural mechanisms of stimulus-specific control associations, and they significantly extend current conceptions of the type of learning processes mediated by the caudate.