Miracle-dz/UniFAR-FTUs huggingface dataset:
Rationale and protocol of the MetNET-1 trial, a prospective, single center, phase II study to evaluate the activity and safety of everolimus in combination with octreotide LAR and metformin in patients with advanced pancreatic neuroendocrine tumors

Abnormal PI3K-AKT-mTOR pathway signalling and autocrine activation of the mTOR pathway, mediated through insulin-like growth factor-1, have been implicated in the proliferation of pancreatic neuroendocrine tumor (pNET) cells. Everolimus, an mTOR inhibitor, has shown antitumor benefit in pNETs alone and in combination with octreotide LAR in RADIANT-1 and RADIANT-3 studies. Although everolimus-based phase II/III trials have improved progression-free survival for pNET, its use has not impacted on prolonging overall survival. Metformin has recently shown some anti-cancer activity in both in vitro and in vivo studies by its indirect properties to decrease insulin and insulin-like growth factor-1 (IGF-1) levels and by its antitumour effect to promote AMPK activation and consequently inhibition to TSC1–2/mTOR complex. In light of even more retrospective evidence of metformin's anticancer activity, a prospective evaluation is required to either confirm or discard these preliminary findings. With the aim to evaluate the antiproliferative effect of metformin in combination with everolimus and octreotide LAR in pancreatic well-differentiated neuroendocrine tumor patients, a single arm, prospective, single center phase II study was designed (MetNET-1 trial, NCT 02294006). Forty-three patients are expected to be evaluated. The study is ongoing, and recruitment is estimated to be completed in August 2016. The results will be anticipated in 2017.
Extracellular sheets and tunnels modulate glutamate diffusion in hippocampal neuropil

Although the extracellular space in the neuropil of the brain is an important channel for volume communication between cells and has other important functions, its morphology on the micron scale has not been analyzed quantitatively owing to experimental limitations. We used manual and computational techniques to reconstruct the 3D geometry of 180 μm3 of rat CA1 hippocampal neuropil from serial electron microscopy and corrected for tissue shrinkage to reflect the in vivo state. The reconstruction revealed an interconnected network of 40–80 nm diameter tunnels, formed at the junction of three or more cellular processes, spanned by sheets between pairs of cell surfaces with 10–40 nm width. The tunnels tended to occur around synapses and axons, and the sheets were enriched around astrocytes. Monte Carlo simulations of diffusion within the reconstructed neuropil demonstrate that the rate of diffusion of neurotransmitter and other small molecules was slower in sheets than in tunnels. Thus, the non‐uniformity found in the extracellular space may have specialized functions for signaling (sheets) and volume transmission (tunnels). J. Comp. Neurol. 521:448–464, 2013. © 2012 Wiley Periodicals, Inc.
A systematic review of patients', parents' and healthcare professionals' adrenaline auto-injector administration techniques

Introduction In order to enable fast treatment response to anaphylactic reactions, adrenaline auto-injectors (AAI) have been developed and manufactured. It has been reported in several studies that administration technique is suboptimal. The primary purpose of this study was to review the nature and extent of the deficiencies in administration technique among patients, parents/caregivers and healthcare professionals. Methods Relevant publications were identified between 1998 and 2015 using two search methods: a keyword search in Embase, PubMed, British Nursing Index and Cumulative Index to Nursing and Allied Health Literature and a search of reference lists of relevant articles. Results Twenty-three studies met the inclusion criteria. Overall, 37% of patients, 32% of parents/caregivers and 21% of healthcare professionals demonstrated correct administration technique. For studies which employed a before-and-after training study design, correct technique was achieved in 77% of patients, 79% of caregivers and 65% of healthcare professionals. The most consistently observed error was the failure to hold the device in place for the recommended time. For patients, factors associated with good technique were being aged over 18 years, trained in AAI administration by an allergist, prescribed an AAI for more than 30 months, having a history of severe anaphylaxis and membership of a support group. For parents/caregivers in addition to those mentioned, being given a training device with which to practice, improved technique. Discussion There was wide variation in administration techniques reported. However, studies designed using before-and-after training show that even a brief demonstration and educational intervention can improve technique. Further studies are required to design and pilot acceptable and cost-effective educational materials.
An Annotation System for Development of Chinese Discourse Corpus

Well-annotated discourse corpora facilitate the discourse researches. Unlike English, the Chinese discourse corpus is not widely available yet. In this paper, we present a webbased annotation system to develop a Chinese discourse corpus with much finer annotation. We first review our previous corpora from the practical point of view, then propose a flexible annotation framework, and finally demonstrate the web-based annotation system. Under the proposed annotation scheme, both the explicit and the implicit discourse relations occurring on various linguistic levels will be captured and labelled with three-level PDTB tags. Besides, the sentiment information of each instance is also annotated for advanced study.
Formal verification of dead code elimination in Isabelle/HOL

Correct compilers are a vital precondition to ensure software correctness. Optimizations are the most error-prone phases in compilers. In this paper, we formally verify dead code elimination (DCE) within the theorem prover Isabelle/HOL. DCE is a popular optimization in compilers which is typically performed on the intermediate representation. In our work, we reformulate the algorithm for DCE so that it is applicable to static single assignment (SSA) form which is a state of the art intermediate representation in modern compilers, thereby showing that DCE is significantly simpler on SSA form than on classical intermediate representations. Moreover, we formally prove our algorithm correct within the theorem prover Isabelle/HOL. Our program equivalence criterion used in this proof is based on bisimulation and, hence, captures also the case of non-termination adequately. Finally we report on our implementation of this verified DCE algorithm in the industrial-strength scale compiler system.
Acute myeloid leukaemia: expression of MYC protein and its association with cytogenetic risk profile and overall survival

Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright © 2016 John Wiley & Sons, Ltd.
The Relaxed-Ring: a Fault-Tolerant Topology for Structured Overlay Networks

Fault-tolerance and lookup consistency are considered crucial properties for building applications on top of structured overlay networks. Many of these networks use the ring topology for the organization or their peers. The network must handle multiple joins, leaves and failures of peers while keeping the connection between every pair of successor-predecessor correct. This property makes the maintenance of the ring very costly and temporarily impossible to achieve, requiring periodic stabilization for fixing the ring. We introduce the relaxed-ring topology that does not rely on a perfect successor-predecessor relationship and it does not need a any periodic maintenance. Leaves and failures are considered as the same type of event providing a fault-tolerant and self-organizing maintenance of the ring. Relaxed-ring's limitations with respect to failure handling are formally identified, providing strong guarantees to develop applications on top of the architecture. Besides permanent failures, the paper analyses temporary failures and false suspicions caused by broken links, which are often ignored.
Antigenic and genetic characterization of serotype G2 human rotavirus strains from South Africa from 1984 to 1998

Within South Africa, cyclic peaks of serotype G2P[4] rotavirus infection have been observed and these strains were prevalent in some locations. To examine the cyclic phenomenon of serotype G2 rotaviruses, historical stool collections from South Africa spanning 15 years were screened for G2 strains. Subgroup (VP6) ELISA, polyacrylamide gel electrophoresis (PAGE), and P genotyping were performed on 43 G2 strains to investigate the associated DS‐1 genogroup characteristics. Antigenic variation of the gene encoding the major neutralization glycoprotein (VP7) was also investigated using G2‐specific monoclonal antibodies. In addition, the VP7 gene of 14 serotype G2 strains was sequenced to examine genetic variation. Serotype G2 strains from South Africa displayed a 10 year cyclic pattern with major epidemics occurring in 1987 and 1997. Serotype G2 strains were also found co‐dominant with G1 strains in 1984, 1990, and 1993. The G2 strains from the major epidemics appeared to have emerged from community strains in a manner similar to that suggested for G1 strains The serotype G2 strains displayed subgroup I specificity and short electropherotypes characteristic of DS‐1 genogroup rotavirus strains but appeared to differ in the VP4 gene. Genetic analyses revealed three major serotype G2 lineages, i.e., strains isolated prior to 1987, strains isolated between 1988 and 1994, and strains isolated from 1995. The use of monoclonal antibodies and PCR primers designed against older G2 strains has resulted in the failure to serotype G2 strains circulating currently. J. Med. Virol. 72:320–327, 2004. © 2004 Wiley‐Liss, Inc.
Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma.

PURPOSE To evaluate tumor response, pharmacodynamic effects, and safety of a combination of lomeguatrib (LM), an O6-methylguanine DNA-methyltransferase (MGMT) inactivator, and temozolomide (TMZ), TMZ alone, and LM/TMZ after disease progression on TMZ alone in patients with advanced melanoma. PATIENTS AND METHODS Patients with unresectable stage III or IV cutaneous melanoma who had no prior systemic chemotherapy were randomly assigned to receive either 40 to 80 mg LM and 125 mg/m2 TMZ or 200 mg/m2 TMZ on days 1 through 5 of each 28-day treatment cycle. Drugs were administered orally for up to six cycles of treatment. Patients on TMZ alone were offered LM/TMZ at progression, if fit enough to receive treatment. RESULTS One hundred four patients were enrolled, with 52 in each trial arm. Twenty-seven TMZ-treated patients received LM/TMZ after progression on TMZ. Unexpectedly, analysis of tumor biopsies showed rapid recovery of MGMT after LM/TMZ with 40 mg/d LM. Therefore, doses of LM were escalated to 60 then 80 mg/d. Tumor response rates were 13.5% with LM/TMZ and 17.3% with TMZ alone. No patient responded to LM/TMZ having progressed through TMZ. Median time to disease progression was 65.5 days for LM/TMZ and 68 days for TMZ. All treatments were well tolerated, although hematologic and gastrointestinal adverse events were common. A higher incidence of hematological adverse events was observed in the LM/TMZ combination arm. CONCLUSION The efficacy of LM and TMZ in the current dosing schedule is similar to that of TMZ alone. To maintain MGMT depletion in tumor dosing of LM needs to be continued beyond that of TMZ.
Aging, Culture, and Memory for Socially Meaningful Item-Context Associations: An East-West Cross-Cultural Comparison Study

Research suggests that people in Eastern interdependent cultures process information more holistically and attend more to contextual information than do people in Western independent cultures. The current study examined the effects of culture and age on memory for socially meaningful item-context associations in 71 Canadians of Western European descent (35 young and 36 older) and 72 native Chinese citizens (36 young and 36 older). All participants completed two blocks of context memory tasks. During encoding, participants rated pictures of familiar objects. In one block, objects were rated either for their meaningfulness in the independent living context or their typicality in daily life. In the other block, objects were rated for their meaningfulness in the context of fostering relationships with others or for their typicality in daily life. The encoding in each block was followed by a recognition test in which participants identified pictures and their associated contexts. The results showed that Chinese outperformed Canadians in context memory, though both culture groups showed similar age-related deficits in item and context memory. The results suggest that Chinese are at an advantage in memory for socially meaningful item-context associations, an advantage that continues from young adulthood into old age.
The gradient effect of context on language switching and lexical access in bilingual production

ABSTRACT Previous research on bilingual language switching costs has demonstrated asymmetrical switch costs, driven primarily by language dominance, such that switches into a more dominant language incur significantly greater reaction time delays than switches into a less dominant language. While such studies have generally relied on a fixed ratio of switch to nonswitch tokens, it is clear that bilinguals operate not in a fixed ratio, but along a naturally occurring bilingual continuum of modes or contexts. Bridging the concepts of language switching and language context, the current study examines language switching costs through a cued picture-naming study with variable contexts or modes. The results demonstrate that switch costs are dependent upon both language dominance and language context, with asymmetrical costs found in more monolingual modes and symmetrical costs found in bilingual modes. Implications are discussed with respect to language mode and gradient inhibitory mechanisms of language selection.
Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

ABSTRACT The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens.
Study on the Relationship between Profile Images and User Behaviors on Twitter

In recent years, many researchers have studied the characteristics of Twitter, which is a microblogging service used by a large number of people worldwide. However, to the best of our knowledge, no study has yet been conducted to study the relationship between profile images and user behaviors on Twitter. We assume that the profile images and behaviors of users are influenced by their internal properties, because users consider their profile images as symbolic representations of themselves on Twitter. We empirically categorized profile images into 13 types, and investigated the relationships between each category of profile images and users' behaviors on Twitter.
Alice's Adventure's in New Media: An Exploration of Interactive Narratives in Augmented Reality

Alice’s Adventures in New Media is an Augmented Reality (AR) experience based on A Mad Tea Party, a chapter from Lewis Carroll’s book Alice’s Adventures in Wonderland. The user assumes the role of Alice and sits at the tea party with three interactive characters: the Mad Hatter, the Dormouse, and the March Hare. The video-based characters are presented through a head-mounted display, and appear to be seated at the same physical table as the user. As a developing medium, AR has yet to establish itself as a narrative form. By comparing the unique characteristics of AR with established media, the project explores AR as a storytelling medium. Innovations include the refashioning of older media (such as film) for the development of an AR narrative, the use of simple procedural characters to create an immersive interactive experience, and the development of tools that enable the production of AR experiences.
SALSA: A Framework for Dynamic Configuration of Cloud Services

Contemporary cloud services are constructed from different types of software and deployed on multiple cloud infrastructures, which offer various configuration options, and can change dynamically at runtime. Due to this complexity, such cloud services require substantial configuration efforts. Currently we lack techniques for automating the complex tasks and providing fine-grained configuration features for multi-cloud services. In this paper, we present a novel multi-level configuration approach for complex cloud services on multi-cloud environments. We develop techniques for automating configuration orchestration activities. Our solution enables the fine-grained configuration at different application abstraction levels and supports the dynamic change of cloud services at runtime. We provide the SALSA framework to implement our approach and demonstrate its usefulness with several real-world services.
Non-iterative privacy preservation for online lotteries

Unlike gambling, lottery games can exist in a lawful form to raise funds for charitable institutions. Owing to the expeditious development of network technology, lotteries over the Internet have become an inevitable trend. Since the Internet allows people to communicate with each other without direct contact, it is more difficult to guarantee the security and fairness of online lotteries than for conventional lottery games. However, electronic lottery methods can also provide something that conventional lottery mechanisms cannot: they allow players to purchase tickets at any time and in any place where they can access the Internet. The authors propose an online lottery mechanism that can confirm the propositions of general lottery games. Specifically, this novel method not only allows players to make t-out-of-n numbers in lotteries without iterative selection but also preserves the privacy of players' choices, making the system more similar to traditional lottery games.
Amalgam Tooth Fillings and Man's Mercury Burden

Next to nutrition, amalgam fillings represent the main source for exposure of the general population to mercury. Toxicological considerations focus on the dose of mercury resulting from such exposure. Various approaches to estimate this dose are reviewed. Introducing the dose into the known toxicokinetic model for mercury, tissue and blood and urine concentrations related to mercury release from the fillings can be predicted. These agree well with autopsy and in vivo observations. An assessment of the health hazard for individuals with amalgam fillings shows that the combined mercury intake from food and amalgam does not exceed the acceptable daily intake. In addition, blood and urine mercury concentrations of amalgam bearers are below one tenth of the critical values associated with the onset of early symptoms or of subclinical effects attributable to mercury.
Crystal structure of 1-ethyl-5-iodoindolin-2-one

Molecules of 1-ethyl-5-iodoindolin-2-one are arranged in columns extending along the a axis and interact with the molecules in adjacent columns via intermolecular C—H⋯O hydrogen bonds and I⋯I short contacts. A one-dimensional zigzag iodine chain along the a axis can be recognized between two neighbouring columns.
A Single Dominant Gene for Resistance to the Soybean Aphid in the Soybean Cultivar Dowling

The soybean aphid (Aphis glycines Matsumura), a new pest of soybean [Glycine max (L.) Merr. ], rapidly spread throughout North America after its arrival in 2000 and caused millions of dollars in economic losses. At present, the application of insecticides is the only means to control the soybean aphid. However, genetic resistance to the aphid was recently discovered in soybean germplasm and the soybean cultivar Dowling was identified as having strong antibiosis-type aphid resistance. The objective of this study was to determine the inheritance of resistance to the soybean aphid in Dowling. Resistance in F1 ,F 2, and F2–derived F3 (F2:3) families from crosses between Dowling and the two susceptible soybean cultivars Loda and Williams 82 was analyzed. All F1 plants were resistant to the aphid. Heterogeneity of segregation of F2 plants in 14 Dowling 3 Loda F2 families was nonsignificant (P 5 0.16), and pooled F2 data, with 132 resistant to 45 susceptible plants, fit a 3:1 ratio (P 5 0.90). F2 plants from Dowling 3 Williams 82 segregated 135 resistant to 44 susceptible, also fitting a 3:1 ratio (P 5 0.89). Segregation among the F2:3 families fit a 1:2:1 monogenic inheritance pattern. These results indicated that a single dominant gene named Rag1 controlled resistance in Dowling. The monogenic dominant nature of resistance will enable breeders to rapidly convert existing susceptible cultivars to resistant cultivars using backcrossing procedures.