bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration
Authors: Balikova Irina , Postelmans Laurence , Pasteels Brigitte , Coquelet Pascale , Catherine Janet , Efendic Azra , Hosoda Yoshikatsu , Miyake Masahiro , Yamashiro Kenji ,   ANGEL study group members, Thienpont Bernard , Lambrechts Diether 
Published: December 2019

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.
Variation in exposure to endoscopic haemostasis for acute upper gastrointestinal bleeding during UK gastroenterology training
Authors: Siau Keith , Morris A John , Murugananthan Aravinth , McKaig Brian , Dunckley Paul 
Published: December 2019

IntroductionGastroenterologists are typically expected to be competent in endoscopic haemostasis for acute upper gastrointestinal bleeding (AUGIB), with the Certificate of Completion of Training (CCT) often heralding the onset of participation in on-call AUGIB rotas. We analysed the volume of haemostasis experience recorded by gastroenterology CCT holders on the Joint Advisory Group on Gastrointestinal Endoscopy Training System (JETS) e-portfolio, the UK electronic portfolio for endoscopy, and assessed for variations in exposure to haemostasis.MethodsUK gastroenterologists awarded CCT between April 2014 and April 2017 were retrospectively identified from the specialist register. Credentials were cross-referenced with JETS to retrieve AUGIB haemostasis procedures prior to CCT. Procedures were collated according to variceal versus non-variceal therapies and compared across training deaneries.ResultsOver the 3-year study period, 241 gastroenterologists were awarded CCT. 232 JETS e-portfolio users were included for analysis. In total, 12 932 haemostasis procedures were recorded, corresponding to a median of 42 (IQR 21–71) per gastroenterologist. Exposure to non-variceal modalities (median 28, IQR 15–52) was more frequent than variceal therapies (median 11, IQR 5–22; p<0.001). By procedure, adrenaline injection (median 12, IQR 6–23) and variceal band ligation (median 10, IQR 5–20) were most commonly recorded, whereas sclerotherapy experience was rare (median 0, IQR 0–1). Exposure to haemostasis did not differ by year of CCT (p=0.130) but varied significantly by deanery (p<0.001), with median procedures ranging from 20–126.ConclusionExposure to AUGIB haemostasis during UK gastroenterology training varied across deaneries and procedural modalities which should prompt urgent locoregional review of access and delivery of training. Endoscopy departments should ensure the availability of supportive provisions in haemostasis (i.e. training/upskilling, supervision, mentorship) during the early post-CCT period.
Randomised evaluation of government health programmes does present a challenge to standard research ethics frameworks
Authors: Watson Samuel I , Dixon-Woods Mary , Lilford Richard J 
Published: December 2019

AbstractIn a recent issue of Journal of Medical Ethics (JME), we discussed the ethical review of evaluations of interventions that would occur whether or not the evaluation was taking place. We concluded that standard research ethics frameworks including the Ottawa Statement, which requires justification for all aspects of an intervention and its roll-out, were a poor guide in this area. We proposed that a consideration of researcher responsibility, based on the consequences of the research taking place, would be a more appropriate way delineate the scope of research ethics review. Weijer and Taljaard present a counterargument to our proposal, which we address in this reply. They claim that a focus on researcher responsibility will weaken the protection of research participants and link it to ‘unethical research’ and a ‘government experimenting on its own people’. However, the moral responsibility of researchers is defined in terms of the consequences of the research on human welfare and harm, not in opposition to it. Weijer and Taljaard argue that researchers must justify what they are studying whether or not they have any control over it and that governments must justify their programmes, including by demonstrating equipoise, to a research ethics committee if they implement them in a randomised way. We strongly disagree that this is a defensible way to define the scope of research ethics review and argue that this provides no further protections to research participants beyond what we propose, but places a potential barrier to learning from government programmes.
Immune modulation by chronic exposure to waterpipe smoke and immediate-early gene regulation in murine lungs
Authors: Reyes-Caballero Hermes , Park Bongsoo , Loube Jeffrey , Sanchez Ian , Vinayachandran Vinesh , Choi Youngshim , Woo Juhyung , Edwards Justin , Brinkman Marielle C , Sussan Thomas , Mitzner Wayne , Biswal Shyam 
Published: December 2019

ObjectiveWe investigated the effects of chronic waterpipe (WP) smoke on pulmonary function and immune response in a murine model using a research-grade WP and the effects of acute exposure on the regulation of immediate-early genes (IEGs).MethodsWP smoke was generated using three WP smoke puffing regimens based on the Beirut regimen. WP smoke samples generated under these puffing regimens were quantified for nicotine concentration. Mice were chronically exposed for 6 months followed by assessment of pulmonary function and airway inflammation. Transcriptomic analysis using RNAseq was conducted after acute exposure to characterise the IEG response. These biomarkers were then compared with those generated after exposure to dry smoke (without water added to the WP bowl).ResultsWe determined that nicotine composition in WP smoke ranged from 0.4 to 2.5 mg per puffing session. The lung immune response was sensitive to the incremental severity of chronic exposure, with modest decreases in airway inflammatory cells and chemokine levels compared with air-exposed controls. Pulmonary function was unmodified by chronic WP exposure. Acute WP exposure was found to activate the immune response and identified known and novel IEG as potential biomarkers of WP exposure.ConclusionChronic exposure to WP smoke leads to immune suppression without significant changes to pulmonary function. Transcriptomic analysis of the lung after acute exposure to WP smoke showed activation of the immune response and revealed IEGs that are common to WP and dry smoke, as well as pools of IEGs unique to each exposure, identifying potential biomarkers specific to WP exposure.
Learning Graphs from Noisy Epidemic Cascades
Authors: Hoffmann Jessica , Caramanis Constantine 
Published: December 2019

Epidemic models accurately represent (among other processes) the spread of diseases, information (rumors, viral videos, news stories, etc.), the spread of malevolent agents in a network (computer viruses, malicious apps, etc.), or even biological processes (pathways in cell signaling networks, chains of activation in the gene regulatory network, etc.). We focus on epidemics that spread on an underlying graph [5].
Most settings assume we know the underlying graph and aim to study properties of the spread. Much work has been done in detection, where the goal is to decide whether or not there is indeed an infection. This problem is of importance in deciding whether or not a computer network is under attack, for instance, or whether a product gets sold through word-of-mouth or thanks to the advertisement campaign (or both). More specifically, the problem of source detection or obfuscation has been extensively studied. On the other side of the spectrum, both experimental and theoretical work has tackled the problem of modeling, predicting the growth, and controlling the spread of epidemics.
Optimizing the Cost of Executing Mixed Interactive and Batch Workloads on Transient VMs
Authors: Ambati Pradeep , Irwin David 
Published: December 2019

Container Orchestration Platforms (COPs), such as Kubernetes, are increasingly used to manage large-scale clusters by automating resource allocation between applications encapsulated in containers. Increasingly, the resources underlying COPs are virtual machines (VMs) dynamically acquired from cloud platforms. COPs may choose from many different types of VMs offered by cloud platforms, which differ in their cost, performance, and availability. While transient VMs cost significantly less than on-demand VMs, platforms may revoke them at any time, causing them to become unavailable. While transient VMs' price is attractive, their unreliability is a problem for COPs designed to support mixed workloads composed of, not only delay-tolerant batch jobs, but also long-lived interactive services with high availability requirements.
To address the problem,we design TR-Kubernetes, a COP that optimizes the cost of executing mixed interactive and batch workloads on cloud platforms using transient VMs. To do so, TR-Kubernetes enforces arbitrary availability requirements specified by interactive services despite transient VM unavailability by acquiring many more transient VMs than necessary most of the time, which it then leverages to opportunistically execute batch jobs when excess resources are available. When cloud platforms revoke transient VMs, TR-Kubernetes relies on existing Kubernetes functions to internally revoke resources from batch jobs to maintain interactive services' availability requirements. We show that TR-Kubernetes requires minimal extensions to Kubernetes, and is capable of lowering the cost (by 53%) and improving the availability (99.999%) of a representative interactive/batch workload on Amazon EC2 when using transient compared to on-demand VMs.
Information, Memory and Capacity in Dynamic Resource Allocation
Authors: Xu Kuang , Zhong Yuan 
Published: December 2019

We propose a general framework, dubbed Stochastic Processing under Imperfect Information (SPII), to study the impact of information constraints and memories on dynamic resource allocation. The framework involves a Stochastic Processing Network (SPN) scheduling problem in which the decision maker may access the system state only through a noisy channel, and resource allocation decisions must be carried out through the interaction between an encoding policy (who observes the state) and allocation policy (who chooses the allocation). Applications in the management of large-scale data centers and human-in-the-loop service systems are among our chief motivations.
We quantify the degree to which information constraints reduce the size of the capacity region in general SPNs, and how such reduction depends on the amount of memories available. Using a novel metric, capacity factor, our main theorem characterizes the reduction in capacity region (under "optimal" policies) for all nondegenerate channels, and across almost all combinations of memory sizes. Notably, the theorem demonstrates, in substantial generality, that (1) the presence of a noisy channel always reduces capacity, (2) more memories for the allocation policy always improve capacity, and (3) more memories for the encoding policy have little to no effect on capacity. Finally, all of our positive (achievability) results are established through constructive, implementable policies.
Our proof program involves the development of a host of new techniques by combining ideas from information theory, learning and queueing theory. We create a simple yet powerful generalization of the Max-Weight policy, in which individual Markov chains are selected dynamically, in a manner analogous to how schedules are used in a conventional Max-Weight policy.
TeksDB
Authors: Han Youil , Kim Bryan S. , Yeon Jeseong , Lee Sungjin , Lee Eunji 
Published: December 2019

Key-value stores (KVS) are now an integral part of modern dataintensive systems. thanks to its simplicity, scalability, and efficiency over traditional database systems. Databases such as MySQL employ KVS (in this case, RocksDB as their backend storage instead of conventional database engines because KVS is less affected by data fragmentation. OLAP and big data analytics applications often use KVS as the backend store to make use of the efficient range_query operations of LSM(Log Structured Merge Tree)-based KVS. Furthermore, the increasing use of KVS as backend stores in distributed systems diversifies the workload for each local KVS, making it necessary to design a highly-concurrent data store that simultaneously processes mixed operations.
The underlying technology trends also put immense pressure on the design of KVS. Nowadays, many core servers with hundred GBs of memory are common in production environments, and this enhanced density of hardware technologies (both in terms of the number of cores and memory capacity) leads to more data items residing in memory. This phenomenon places greater emphasis on the efficiency of the in-memory data structure in KVS, as more data accesses are serviced from its memory component, which is often called the memtable. The current memtable structure of KVS, however, generally assumes a limited memory capacity that only serves as a temporary write buffer, and the use of single-threaded writes or unscalable data structures for the memtable fails to fulfill this external demand.
HyperBench
Authors: Wei Song , Zhang Kun , Tu Bibo 
Published: December 2019

Virtualization is ubiquitous in modern data centers. By deploying applications on separate virtual machines hosted in a shared physical machine, it brings benefits over traditional systems in resources utilization[5, 10], system security[2, 3], and server management[7].
Despite the adoption and these advantages of virtualization, cloud providers, tenants, and developers face different challenges. The hardware and software options to build a virtualization platform pose a challenge for cloud providers. A variety of virtualization platforms make it difficult for tenants to make a choice. Developers are forced to continually improve the architecture and hypervisor design to better support virtual machines. In this context, evaluating the virtualization capabilities of different platforms is necessary.
Visions and challenges in GeoAI, ethics, and spatial quantum computing
Authors: Züfle Andreas 
Published: December 2019

Geographic information systems are changing rapidly as new technologies, such as advances in artificial intelligence and quantum computing, proliferate. Towards gaining a glimpse of possible new directions for the next decades, it is paramount to disseminate and discuss new research directions, challenges, and visions, that may be of broad interest to the SIGSPATIAL community. In the last few years, our community has excelled at providing a forum for such visions and challenges in dedicated
Vision and Challenge
tracks, leading to many visionary research directions [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21]. A goal of this newsletter is to continue and complement these visions. Three vision and challenge topics are covered in this special issue:

1. the first article is contributed by the organizers of GeoAI, the most successful ACM SIGSPATIAL Workshop of the last years, having 40+ registrations each year, and having 50+ people in the workshop room at a time. The authors survey and summarize the directions of GeoAI publications of the last three years, and provide a list of open research directions for this rapidly advancing field;
2. in the second article, Fu et al. discuss ethical issues of mining urban spatial data. They identify ethical vulnerabilities from three primary research directions of urban computing: urban safety analysis, urban transportation analysis, and social media analysis for urban events;
3. in the third article, Martin Werner introduces central aspects of quantum algorithms and explores future directions on how quantum algorithms can be used to leverage spatial and spatio-temporal algorithms. This article describes example algorithms, such as map coloring and dynamic time warping, which may benefit from advances in quantum computing.
Bit complexity for critical point computation in smooth and compact real hypersurfaces
Authors: Elliott Jesse , Schost Éric 
Published: December 2019

Consider the polynomial mapping defined by the projection to the first coordinate on a real, smooth and compact hypersurface. The critical points of this mapping in generic coordinates have several applications in real algebraic geometry. We provide bit complexity estimates for computing them.
Generic coordinates are obtained by applying a randomly chosen linear change of variables to the polynomial defining the hypersurface. The coordinates are sufficiently generic when the Jacobian matrix of the system under study has full rank at the critical points and when the number of critical points is finite. We have proven a new quantitative extension of Thom's weak transversality theorem [1]. By applying this extension, we are able to choose sufficiently generic changes of variables with arbitrarily high probability.
MRI Tumor Regression Grade and Circulating Tumor DNA as Complementary Tools to Assess Response and Guide Therapy Adaptation in Rectal Cancer
Authors: Khakoo Shelize , Carter Paul David , Brown Gina , Valeri Nicola , Picchia Simona , Bali Maria Antonietta , Shaikh Ridwan , Jones Thomas , Begum Ruwaida , Rana Isma , Wotherspoon Andrew , Terlizzo Monica , von Loga Katharina , Kalaitzaki Eleftheria , Saffery Claire , Watkins David , Tait Diana , Chau Ian , Starling Naureen , Hubank Michael , Cunningham David 
Published: December 2019

Abstract

Purpose:
Response to preoperative chemo-radiotherapy (CRT) varies. We assessed whether circulating tumor DNA (ctDNA) might be an early indicator of tumor response or progression to guide therapy adaptation in rectal cancer.

Experimental Design:
A total of 243 serial plasma samples were analyzed from 47 patients with localized rectal cancer undergoing CRT. Up to three somatic variants were tracked in plasma using droplet digital PCR. RECIST and MRI tumor regression grade (mrTRG) evaluated response. Survival analyses applied Kaplan–Meier method and Cox regression.

Results:
ctDNA detection rates were: 74% (n = 35/47) pretreatment, 21% (n = 10/47) mid CRT, 21% (n = 10/47) after completing CRT, and 13% (n = 3/23) after surgery. ctDNA status after CRT was associated with primary tumor response by mrTRG (P = 0.03). With a median follow-up of 26.4 months, metastases-free survival was shorter in patients with detectable ctDNA after completing CRT [HR 7.1; 95% confidence interval (CI), 2.4–21.5; P &lt; 0.001], persistently detectable ctDNA pre and mid CRT (HR 3.8; 95% CI, 1.2–11.7; P = 0.02), and pre, mid, and after CRT (HR 11.5; 95% CI, 3.3–40.4; P &lt; 0.001) compared with patients with undetectable or nonpersistent ctDNA. In patients with detectable ctDNA, a fractional abundance threshold of ≥0.07% mid CRT or ≥0.13% after completing CRT predicted for metastases with 100% sensitivity and 83.3% specificity for mid CRT and 66.7% for CRT completion. All 3 patients with detectable ctDNA post-surgery relapsed compared with none of the 20 patients with undetectable ctDNA (P = 0.001).

Conclusions:
ctDNA identified patients at risk of developing metastases during the neoadjuvant period and post-surgery, and could be used to tailor treatment.
Intratumoral Plasmid IL12 Electroporation Therapy in Patients with Advanced Melanoma Induces Systemic and Intratumoral T-cell Responses
Authors: Greaney Samantha K. , Algazi Alain P. , Tsai Katy K. , Takamura Kathryn T. , Chen Lawrence , Twitty Christopher G. , Zhang Li , Paciorek Alan , Pierce Robert H. , Le Mai H. , Daud Adil I. , Fong Lawrence 
Published: December 2019

AbstractWhereas systemic IL12 is associated with potentially life-threatening toxicity, intratumoral delivery of IL12 through tavokinogene telseplasmid electroporation (tavo) is safe and can induce tumor regression at distant sites. The mechanism by which these responses are mediated is unknown but is presumed to result from a cellular immune response. In a phase II clinical trial of tavo (NCT01502293), samples from 29 patients with cutaneous melanoma with in-transit disease were assessed for immune responses induced with this treatment. Within the blood circulating immune cell population, we found that the frequencies of circulating PD-1+ CD4+ and CD8+ T cells declined with treatment. Circulating immune responses to gp100 were also detected following treatment as measured by IFNγ ELISpot. Patients with a greater antigen-specific circulating immune response also had higher numbers of CD8+ T cells within the tumor. Clinical response was also associated with increased intratumoral CD3+ T cells. Finally, intratumoral T-cell clonality and convergence were increased after treatment, indicating a focusing of the T-cell receptor repertoire. These results indicated that local treatment with tavo can induce a systemic T-cell response and recruit T cells to the tumor microenvironment.
The Blood of Others
Authors: de Saint Aubert Emmanuel , McWeeny Jennifer 
Published: December 2019

Abstract
The author argues, with reference to a number of Merleau-Ponty’s unpublished manuscripts, that the philosopher’s notion of encroachment (empiétement) has origins in Simone de Beauvoir’s 1945 novel The Blood of Others. He examines how the two philosophers approach the encroachment of freedoms, the political stance of pacifism, and the interpretation of Voltaire’s Candide (Part I). The impact of Élisabeth Lacoin’s death on Beauvoir’s and Merleau-Ponty’s philosophies, as well as their relationships with Jean-Paul Sartre is also considered (Part II).