bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Privacy
Authors: Ebadi Hamid , Sands David , Schneider Gerardo 
Published: May 2015

Differential privacy provides a way to get useful information about sensitive data without revealing much about any one individual. It enjoys many nice compositionality properties not shared by other approaches to privacy, including, in particular, robustness against side-knowledge.
Designing differentially private mechanisms from scratch can be a challenging task. One way to make it easier to construct new differential private mechanisms is to design a system which allows more complex mechanisms (programs) to be built from differentially private building blocks in principled way, so that the resulting programs are guaranteed to be differentially private by construction.
This paper is about a new accounting principle for building differentially private programs. It is based on a simple generalisation of classic differential privacy which we call Personalised Differential Privacy (PDP). In PDP each individual has its own personal privacy level. We describe ProPer, a interactive system for implementing PDP which maintains a privacy budget for each individual. When a primitive query is made on data derived from individuals, the provenance of the involved records determines how the privacy budget of an individual is affected: the number of records derived from Alice determines the multiplier for the privacy decrease in Alice's budget. This offers some advantages over previous systems, in particular its fine-grained character allows better utilisation of the privacy budget than mechanisms based purely on the concept of global sensitivity, and it applies naturally to the case of a live database where new individuals are added over time.
We provide a formal model of the ProPer approach, prove that it provides personalised differential privacy, and describe a prototype implementation based on McSherry's PINQ system.
Predicting Program Properties from "Big Code"
Authors: Raychev Veselin , Vechev Martin , Krause Andreas 
Published: May 2015

We present a new approach for predicting program properties from massive codebases (aka "Big Code"). Our approach first learns a probabilistic model from existing data and then uses this model to predict properties of new, unseen programs.
The key idea of our work is to transform the input program into a representation which allows us to phrase the problem of inferring program properties as structured prediction in machine learning. This formulation enables us to leverage powerful probabilistic graphical models such as conditional random fields (CRFs) in order to perform joint prediction of program properties.
As an example of our approach, we built a scalable prediction engine called JSNice for solving two kinds of problems in the context of JavaScript: predicting (syntactic) names of identifiers and predicting (semantic) type annotations of variables. Experimentally, JSNice predicts correct names for 63% of name identifiers and its type annotation predictions are correct in 81% of the cases. In the first week since its release, JSNice was used by more than 30,000 developers and in only few months has become a popular tool in the JavaScript developer community.
By formulating the problem of inferring program properties as structured prediction and showing how to perform both learning and inference in this context, our work opens up new possibilities for attacking a wide range of difficult problems in the context of "Big Code" including invariant generation, decompilation, synthesis and others.
Databases and Programming
Authors: Buneman Peter 
Published: May 2015

The 1990s saw a hugely productive interaction between database and programming language research. Ideas about type systems from programming languages played a central role in generalizing and adapting relational database systems to new data models. At the same time databases provided some of the best concrete examples of the application of concurrency theory and of the benefits of high-level optimization in functional programming languages. One of the driving ambitions behind this research was the idea that database access should be properly embedded in programming languages: one should not have to be bilingual in order to use a database from a programming language; and that goal has to some extent been realized.
In the past fifteen years, new data models, both for data storage and for data exchange have appeared with depressing regularity and with each such model, the inevitable query language. Does programming language research have anything to contribute to these new languages? Should we take the time to to worry about embedding these models in conventional languages? Over the same period, some interesting new connections between databases and programming languages have emerged, notably in the areas of scientific databases, annotation and provenance. Will this provide new opportunities for cross-fertilization?
Ofatumumab Exhibits Enhanced In Vitro and In Vivo Activity Compared to Rituximab in Preclinical Models of Mantle Cell Lymphoma
Authors: Barth Matthew J. , Mavis Cory , Czuczman Myron S. , Hernandez-Ilizaliturri Francisco J. 
Published: May 2015

Abstract
Purpose: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma considered to be incurable with current treatments, including first-line rituximab in combination with multiagent chemotherapy and for those eligible, high-dose chemotherapy and stem cell support or rituximab maintenance. On the other hand, achieving a complete remission by high-sensitive flow cytometry is associated with prolonged duration of remission, stressing the need to develop and/or incorporate novel agents into the management of MCL. To this end, we examined the activity of ofatumumab, an anti-CD20 monoclonal antibody with distinct binding and immunologic properties compared to rituximab, in MCL preclinical models.
Experimental Design: MCL cells were labeled with 51Cr before incubation with rituximab or ofatumumab (10 μg/mL) plus human serum or effector cells. 51Cr-release was measured and the percentage of lysis was calculated. Surface CD20, CD55, and CD59 were measured by Imagestream analysis. SCID mice inoculated subcutaneously with Z138 cells were assigned to control versus four doses of ofatumumab or rituximab (10 mg/kg/dose).
Results: Ofatumumab exhibited enhanced in vitro complement-dependent cytotoxicity activity compared with rituximab in MCL cell lines, despite a high degree of in vitro resistance to rituximab associated with low CD20 levels and/or high expression of complement inhibitory proteins. Ofatumumab also delayed tumor progression and prolonged survival in a murine model of MCL.
Conclusions: Our results demonstrate that ofatumumab is more effective than rituximab in MCL preclinical models, including in the presence of rituximab resistance, and support the clinical investigation of ofatumumab in combination with standard systemic chemotherapy in MCL (NCT01527149). Clin Cancer Res; 21(19); 4391–7. ©2015 AACR.
An Oral Formulation of YK-4-279: Preclinical Efficacy and Acquired Resistance Patterns in Ewing Sarcoma
Authors: Lamhamedi-Cherradi Salah-Eddine , Menegaz Brian A. , Ramamoorthy Vandhana , Aiyer Ramani A. , Maywald Rebecca L. , Buford Adrianna S. , Doolittle Dannette K. , Culotta Kirk S. , O'Dorisio James E. , Ludwig Joseph A. 
Published: May 2015

AbstractEwing sarcoma is a transcription factor–mediated pediatric bone tumor caused by a chromosomal translocation of the EWSR1 gene and one of several genes in the ETS family of transcription factors, typically FLI1 or ERG. Full activity of the resulting oncogenic fusion protein occurs only after binding RNA helicase A (RHA), and novel biologically targeted small molecules designed to interfere with that interaction have shown early promise in the preclinical setting. Herein, we demonstrate marked preclinical antineoplastic activity of an orally bioavailable formulation of YK-4-279 and identify mechanisms of acquired chemotherapy resistance that may be exploited to induce collateral sensitivity. Daily enteral administration of YK-4-279 led to significant delay in Ewing sarcoma tumor growth within a murine model. In advance of anticipated early-phase human clinical trials, we investigated both de novo and acquired mechanism(s) by which Ewing sarcoma cells evade YK-4-279–mediated cell death. Drug-resistant clones, formed by chronic in vitro exposure to steadily increased levels of YK-4-279, overexpressed c-Kit, cyclin D1, pStat3(Y705), and PKC isoforms. Interestingly, cross-resistance to imatinib and enzastaurin (selective inhibitors of c-Kit and PKC-β, respectively), was observed and the use of YK-4-279 with enzastaurin in vitro led to marked drug synergy, suggesting a potential role for combination therapies in the future. By advancing an oral formulation of YK-4-279 and identifying prominent mechanisms of resistance, this preclinical research takes us one step closer to a shared goal of curing adolescents and young adults afflicted by Ewing sarcoma. Mol Cancer Ther; 14(7); 1591–604. ©2015 AACR.
Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer
Authors: Dienstmann Rodrigo , Patnaik Amita , Garcia-Carbonero Rocio , Cervantes Andrés , Benavent Marta , Roselló Susana , Tops Bastiaan B.J. , van der Post Rachel S. , Argilés Guillem , Skartved Niels J.Ø. , Hansen Ulla H. , Hald Rikke , Pedersen Mikkel W. , Kragh Michael , Horak Ivan D. , Braun Stephan , Van Cutsem Eric , Tolcher Anthony W. , Tabernero Josep 
Published: May 2015

Abstract
Tumor growth in the context of EGFR inhibitor resistance may remain EGFR-dependent and is mediated by mechanisms including compensatory ligand upregulation and de novo gene alterations. Sym004 is a two-antibody mixture targeting nonoverlapping EGFR epitopes. In preclinical models, Sym004 causes significant EGFR internalization and degradation, which translates into superior growth inhibition in the presence of ligands. In this phase I trial, we observed grade 3 skin toxicity and hypomagnesemia as mechanism-based dose-limiting events during dose escalation. In dose-expansion cohorts of 9 and 12 mg/kg of Sym004 weekly, patients with metastatic colorectal cancer and acquired EGFR inhibitor resistance were enrolled; 17 of 39 patients (44%) had tumor shrinkage, with 5 patients (13%) achieving partial response. Pharmacodynamic studies confirmed marked Sym004-induced EGFR downmodulation. MET gene amplification emerged in 1 patient during Sym004 treatment, and a partial response was seen in a patient with EGFRS492R mutation that is predictive of cetuximab resistance.
Significance: Potent EGFR downmodulation with Sym004 in patients with metastatic colorectal cancer and acquired resistance to cetuximab/panitumumab translates into significant antitumor activity and validates the preclinical hypothesis that a proportion of tumors remains dependent on EGFR signaling. Further clinical development and expanded correlative analyses of response patterns with secondary RAS/EGFR mutations are warranted. Cancer Discov; 5(6);598–609. ©2015 AACR.
See related commentary by Stintzing and Heinemann, p. 578
This article is highlighted in the In This Issue feature, p. 565
Haploinsufficiency of the NOTCH1 Receptor as a Cause of Adams–Oliver Syndrome With Variable Cardiac Anomalies
Authors: Southgate Laura , Sukalo Maja , Karountzos Anastasios S.V. , Taylor Edward J. , Collinson Claire S. , Ruddy Deborah , Snape Katie M. , Dallapiccola Bruno , Tolmie John L. , Joss Shelagh , Brancati Francesco , Digilio Maria Cristina , Graul-Neumann Luitgard M. , Salviati Leonardo , Coerdt Wiltrud , Jacquemin Emmanuel , Wuyts Wim , Zenker Martin , Machado Rajiv D. , Trembath Richard C. 
Published: May 2015

Background—
Adams–Oliver syndrome (AOS) is a rare disorder characterized by congenital limb defects and scalp cutis aplasia. In a proportion of cases, notable cardiac involvement is also apparent. Despite recent advances in the understanding of the genetic basis of AOS, for the majority of affected subjects, the underlying molecular defect remains unresolved. This study aimed to identify novel genetic determinants of AOS.

Methods and Results—

Whole-exome sequencing was performed for 12 probands, each with a clinical diagnosis of AOS. Analyses led to the identification of novel heterozygous truncating
NOTCH1
mutations (c.1649dupA and c.6049_6050delTC) in 2 kindreds in which AOS was segregating as an autosomal dominant trait. Screening a cohort of 52 unrelated AOS subjects, we detected 8 additional unique
NOTCH1
mutations, including 3 de novo amino acid substitutions, all within the ligand-binding domain. Congenital heart anomalies were noted in 47% (8/17) of
NOTCH1
-positive probands and affected family members. In leukocyte-derived RNA from subjects harboring
NOTCH1
extracellular domain mutations, we observed significant reduction of
NOTCH1
expression, suggesting instability and degradation of mutant mRNA transcripts by the cellular machinery. Transient transfection of mutagenized
NOTCH1
missense constructs also revealed significant reduction in gene expression. Mutant
NOTCH1
expression was associated with downregulation of the Notch target genes
HEY1
and
HES1
, indicating that
NOTCH1
-related AOS arises through dysregulation of the Notch signaling pathway.

Conclusions—

These findings highlight a key role for
NOTCH1
across a range of developmental anomalies that include cardiac defects and implicate
NOTCH1
haploinsufficiency as a likely molecular mechanism for this group of disorders.
Effects of Parental Smoking on Exercise Systolic Blood Pressure in Adolescents
Authors: Hacke Claudia , Weisser Burkhard 
Published: May 2015

Background
In adults, exercise blood pressure seems to be more closely related to cardiovascular risk than resting blood pressure; however, few data are available on the effects of familial risk factors, including smoking habits, on exercise blood pressure in adolescents.

Methods and Results

Blood pressure at rest and during exercise, parental smoking, and other familial risk factors were investigated in 532 adolescents aged 12 to 17 years (14.6±1.5 years) in the Kiel
EX
.
PRESS
. (
EX
ercise
PRESS
ure) Study. Exercise blood pressure was determined at 1.5 W/kg body weight using a standardized submaximal cycle ergometer test. Mean resting blood pressure was 113.1±12.8/57.2±7.1 mm Hg, and exercise blood pressure was 149.9±19.8/54.2±8.6 mm Hg. Parental smoking increased exercise systolic blood pressure (+4.0 mm Hg, 3.1 to 4.9;
P=
0.03) but not resting blood pressure of the subjects (adjusted for age, sex, height, body mass index percentile, fitness). Parental overweight and familial hypertension were related to both higher resting and exercise systolic blood pressure values, whereas associations with an inactive lifestyle and a low educational level of the parents were found only with adolescents' blood pressure during exercise. The cumulative effect of familial risk factors on exercise systolic blood pressure was more pronounced than on blood pressure at rest.

Conclusions
Parental smoking might be a novel risk factor for higher blood pressure, especially during exercise. In addition, systolic blood pressure during a submaximal exercise test was more closely associated with familial risk factors than was resting blood pressure, even in adolescents.
Bayesian Model Averaging with Stratified Sampling for Probabilistic Quantitative Precipitation Forecasting in Northern China during Summer 2010
Authors: Zhu Jiangshan , Kong Fanyou , Ran Lingkun , Lei Hengchi 
Published: May 2015

Abstract
To study the impact of training sample heterogeneity on the performance of Bayesian model averaging (BMA), two BMA experiments were performed on probabilistic quantitative precipitation forecasts (PQPFs) in the northern China region in July and August of 2010 generated from an 11-member short-range ensemble forecasting system. One experiment, as in many conventional BMA studies, used an overall training sample that consisted of all available cases in the training period, while the second experiment used stratified sampling BMA by first dividing all available training cases into subsamples according to their ensemble spread, and then performing BMA on each subsample. The results showed that ensemble spread is a good criterion to divide ensemble precipitation cases into subsamples, and that the subsamples have different statistical properties. Pooling the subsamples together forms a heterogeneous overall sample. Conventional BMA is incapable of interpreting heterogeneous samples, and produces unreliable PQPF. It underestimates the forecast probability at high-threshold PQPF and local rainfall maxima in BMA percentile forecasts. BMA with stratified sampling according to ensemble spread overcomes the problem reasonably well, producing sharper predictive probability density functions and BMA percentile forecasts, and more reliable PQPF than the conventional BMA approach. The continuous ranked probability scores, Brier skill scores, and reliability diagrams of the two BMA experiments were examined for all available forecast days, along with a logistic regression experiment. Stratified sampling BMA outperformed the raw ensemble and conventional BMA in all verifications, and also showed better skill than logistic regression in low-threshold forecasts.
Inherent Predictability, Requirements on the Ensemble Size, and Complementarity
Authors: Kumar Arun , Chen Mingyue 
Published: May 2015

Abstract
Faced with the scenario when prediction skill is low, particularly in conjunction with long-range predictions, a commonly proposed solution is that an increase in ensemble size will rectify the issue of low skill. Although it is well known that an increase in ensemble size does lead to an increase in prediction skill, the general scope of this supposition, however, is that low prediction skill is not a consequence of constraints imposed by inherent predictability limits, but an artifact of small ensemble sizes, and further, increases in ensemble sizes (that are often limited by computational resources) are the major bottlenecks for improving long-range predictions. In proposing that larger ensemble sizes will remedy the issue of low skill, a fact that is not well appreciated is that for scenarios with high inherent predictability, a small ensemble size is sufficient to realize high predictability, while for scenarios with low inherent predictability, much larger ensemble sizes are needed to realize low predictability. In other words, requirements on ensemble size (to realize the inherent predictability) and inherent predictability are complementary variables. A perceived need for larger ensembles, therefore, may also imply the presence of low predictability.
Family functioning, social support, and quality of life for patients with anxiety disorder
Authors: Wang Jikun , Chen Yuhao , Tan Cuicui , Zhao Xudong 
Published: May 2015

Background: Few studies have examined the relationship between family functioning, social support and quality of life in patients with anxiety disorder. There is a paucity of research on anxiety disorders and their predictors in China. Aims: This study aimed to explore family functioning, social support and quality of life for patients with anxiety disorder and examine the relationship between these elements. Methods: A total of 107 patients who met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for anxiety disorder and 80 healthy controls completed the McMaster Family Assessment Device, the Perceived Social Support Scale and the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire. Results: The findings indicate that patients with anxiety disorder in China tend to have poor family functioning and quality of life, as well as a higher subjective perception of social support. There were strong correlations between family functioning, social support and quality of life. Affective involvement and not living with parents were identified as risk factors for anxiety disorders, while a high family income was a protective factor. Conclusion: Anxiety disorder is associated with reduced family functioning and poorer quality of life for Chinese patients. In addition, the Family Assessment Device is a suitable instrument for evaluating family functioning in Chinese patients with anxiety disorder.
A Comparison of Dabigatran With Warfarin for Stroke Prevention in Atrial Fibrillation in an Asian Population
Authors: Yap Lok Bin , Eng Daniel Theng Sheng , Sivalingam Lingghesh , Rusani Beni Isman , Umadevan Dhanan , Muhammad Zulkeflee , Koh Kok Wei , Aisha Barveen , Hashim Mohd Irwan , Rebo Rosila , Hussin Azlan , Kaur Surinder , Shanmugam Rajasingam , Omar Razali 
Published: May 2015

Background: The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke. Methods: A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013. Results: Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of <2. None of the patients in the dabigatran group had ischemic cerebrovascular accident (CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59). Conclusion: There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF.