bluuebunny/crossref_metadata_2025_split huggingface dataset:
VP87 Extrapolation From Progression Free Survival To Overall Survival In Oncology
Authors: Hernandez-Villafuerte Karla , Fischer Alastair , Latimer Nicholas , Henshall Chris 
Published: January 2018

INTRODUCTION:The outcomes from clinical and other healthcare trials of most interest to patients and health systems are usually increases in the quality and length of life (overall survival (OS)). This poses a problem, because complete knowledge on the true increase in OS is not available until the last person in the trial dies. However, if OS is sufficiently correlated with a surrogate endpoint that is observable within the trial period or soon after the treatment has finished, this can be used to estimate OS, without much error. The most widely-used surrogate endpoint in oncology is progression-free survival (PFS). We aim at (i) analyzing the methods used to extrapolate from PFS to OS in the field of oncology; (ii) identifying whether a clear guidance exists in the literature about what is considered to be ‘best practice’ in extrapolation from PFS to OS; (iii) determining the key limitations, weaknesses and gaps in the current literature and method used to test PFS surrogacy.METHODS:We extend the literature review carried out previously (1), we interview experts from regulatory and reimbursement bodies, and we explore academic research into the methodology of surrogacy and the need for better reporting of surrogacy papers.RESULTS:A number of factors affect the relationship between PFS and OS. Therefore, there is no unique correct answer for the question of whether PFS is an appropriate surrogate for OS in oncology. Many of these factors are related to the length and characteristics of post-progression survival (PPS).CONCLUSIONS:Any consideration of evidence relating to PFS should consider both tumour type and other factors, particularly those related to PPS. Protocols of future follow-up of clinical trial patients should specify procedures for gathering information about the effect of post-progression management of the disease. This should allow stronger conclusions to be extracted from statistical analyses. Improved reporting standards will aid in achieving this goal. In addition, it is very likely that increasing the use of IPD will result in greater precision in estimating the benefits of worthwhile drugs.
VP182 Network Amongst The Health Technology Assessment Ecosystem
Authors: Cinaroglu Songul , Baser Onur 
Published: January 2018

INTRODUCTION:There has been a growing interest in international collaboration among Health Technology Assessment (HTA) organizations on macro, meso, and micro policy-making levels. Global member-driven professional HTA societies make contributions to scientific improvement and enhance interactions in the HTA ecosystem. However, little is known about collaboration between HTA organizations at the global level. This study intends to examine the main drivers of network relationships of HTA organizations.METHODS:Social network analysis was used to ascertain the relationships between HTA organizations and to visualize the main drivers of collaboration. The total number of memberships of the HTA organizations of the International Society For Pharmacoeconomics and Outcomes Research (ISPOR), Health Technology Assessment International (HTAi), International Netowork of Agencies for HTA (INAHTA), EuroScan, European Network for HTA (EUnetHTA), HTAsiaLink, Red de Evaluación de Tecnologías en Salud de las Américas (RedETSA) were considered to create the network. Ten different types of HTA organizations were considered in the analysis including the Ministry of Health (MoH), university, for-profit, and hospitals. The Fruchterman-Reingold algorithm was used to perform network analysis; average clustering coefficient and average path length were examined to measure collaborative performance.RESULTS:A network graph of the HTA ecosystem shows the highest collaborative frequency in terms of HTA organizations, occurred with members of the Ministry of Health, government agencies, universities, and non-profit organizations. The average path length was 2.21 and the average clustering coefficient was 36.576 which indicates an obvious clustering effect.CONCLUSIONS:These study results highlight that the network throughout the HTA ecosystem is driven by government organizations. Integrating the private sector into the system, creating common information and data sharing strategies, and improving the number of internationally experienced HTA professionals are essential strategies to foster collaboration in HTA organizations. As HTA is shaped by local dynamics and there is no gold standard for HTA implementation, encouragement of collaborative efforts is the only way to prevent duplication of effort and to make health technologies available for everyone.
VP196 Impact Of Trial Registry Search Features On Searches In CT.gov/ICTRP
Authors: Hausner Elke , Knelangen Marco , Waffenschmidt Siw 
Published: January 2018

INTRODUCTION:In contrast to bibliographic databases, trial registries do not offer the option of formulating complex search queries, thus making targeted searches more difficult. However, ClinicalTrials.gov (CT.gov) and the International Clinical Trials Registry Platform (ICTRP) offer different search features that may help compensate this limitation. Our aim was to determine the importance of search features (for example, searches using synonyms or, additionally in CT.gov, automatic inclusion of further search fields) for trial registry searches.METHODS:We conducted a project called “Trial registry searches for studies of newly approved drugs” (1). One analysis investigated the question as to whether searches for different health conditions and interventions (new drugs) directly identified registry entries with the search terms entered or whether certain search features were responsible for this. We searched CT.gov and ICTRP for different conditions and interventions using the advanced search interface. For each search, we documented the synonyms listed in the two registries. We imported the registry entries into EndNote and evaluated whether the search terms used were available in the corresponding search fields (condition; intervention).RESULTS:For CT.gov, 96 registry entries on 18 interventions and 190 entries on 12 conditions were analysed. Of these, twenty-three (24 percent) entries for interventions and thirty-eight (20 percent) for conditions were identified by search features, not by search terms. For ICTRP, 32 entries on 10 interventions and 100 entries on 9 conditions were analysed. Of these, five (16 percent) entries for interventions and eight (8 percent) for conditions were identified by search features.CONCLUSIONS:Trial registry search features have an important impact on the sensitivity of searches. Many studies are not identified by the search terms entered, but by searches using synonyms and, additionally in CT.gov, by automatic inclusion of further search fields. Moreover, search features in CT.gov are more effective than in ICTRP – even though the same search terms are used, they consistently yield higher sensitivities.
VP200 Untangling What Information Specialists Should Document and Report
Authors: Tjosvold Lisa , Chojecki Dagmara 
Published: January 2018

INTRODUCTION:Thorough documentation and clear reporting are essential when conducting a comprehensive literature search for a health technology assessment (HTA) or systematic review. The ultimate goal of this process is transparency and reproducibility with the added benefit of increasing the reader's confidence in the research. Thorough documentation of the search also allows for critical appraisal of the methodology used and facilitates future updating of a review (1,2).It has been found that large numbers of systematic review searches are inadequately documented and there is little consensus on best practices for reporting standards (3).As part of the SuRe Info Project, we conducted a review of all current reporting standards relevant to HTAs and systematic reviews in addition to looking at the published literature on this topic in order to synthesize the evidence in this area and create a standard set of agreed upon recommendations.METHODS:We conducted a comprehensive search of Medline, Embase, and LISA (Library & Info Studies Abstracts) databases. We also examined the Equator Network (http://www.equator-network.org/) website. Reference lists of included studies and reporting guidelines were also consulted. Eleven reporting guidelines and eight studies were included in the review by two independent reviewers. Anything published before 2006, that was not a research article (other than the guidelines), and/or that did not provide new recommendations (that is, a review of another set of recommendations) was excluded.RESULTS:After collecting data on the suggested reporting elements described in the literature, we pooled our results to create an overarching list of the most commonly recommended elements to describe and the most commonly recommended methods to use when documenting a comprehensive search. Not only did these elements pertain to documenting the search strategy for the final report, but they also pertained to the protocol and the abstract of a review.CONCLUSIONS:It is hoped that this overview of the literature and compilation of the evidence will clarify some of the confusion that seems to exist when documenting and reporting searches and perhaps it will even help to reduce the existence of poorly described strategies in the research literature.
VP203 Performance Evaluation Of Eye-Tracking Devices
Authors: Recalde Luciano , Núñez José , Yegros César , Villegas Carolina 
Published: January 2018

INTRODUCTION:There are different devices, systems and technologies for people with disabilities. It's necessary to provide information on the effectiveness of products in the market and competitiveness in terms of price-quality, and providing an endorsement in the acquisition of technologies that improve their quality of life. The use of eye tracking devices is growing and its implementation in different areas has attracted the attention of several developers. Therefore the need to generate a product that evaluates the functionality of such devices is necessary in order to avoid unnecessary expenses when acquiring or repairing one of these devices.METHODS:An interface was created with different functionalities such as the location of the coordinates in which the pointer is located, standardized graphic interface design to provide statistical data that allow an objective result for its subsequent analysis and an endless number of design possibilities.The tests performed were of accuracy and precision where the subject was asked to follow the instructions given and observe a sequence of points, especially the points located at the ends of the monitor as these are the critical points in which there is less coincidence between the cursor and the gaze.RESULTS:The results obtained provided information on the performance of the tracking device. In this way it was possible to establish that the accuracy of the ocular tracker: it was ± 12.83 pixels on the horizontal axis and ± 10.66 pixels on the vertical axis. The precision was ± 9.8 pixels on the horizontal axis and ± 14.23 pixels on the vertical axis.This shows the use phenomenon caused due to the limited mobility of the eyes in the vertical axis in comparison to the horizontal mobility. The precision data obtained indicate that, because the movement on the vertical axis is smaller, there is a less continuous spectrum of positions on the axis, which translates to less precision.CONCLUSIONS:The data obtained can be used to compare with the results of the test with other eye tracking devices and thus this could serve as a tool to select an eye tracking device according to the user's need and his economical capabilities.
Designable and dynamic single-walled stiff nanotubes assembled from sequence-defined peptoids
Authors: Jin Haibao , Ding Yan-Huai , Wang Mingming , Song Yang , Liao Zhihao , Newcomb Christina J. , Wu Xuepeng , Tang Xian-Qiong , Li Zheng , Lin Yuehe , Yan Feng , Jian Tengyue , Mu Peng , Chen Chun-Long 
Published: January 2018

AbstractDespite recent advances in the assembly of organic nanotubes, conferral of sequence-defined engineering and dynamic response characteristics to the tubules remains a challenge. Here we report a new family of highly designable and dynamic nanotubes assembled from sequence-defined peptoids through a unique “rolling-up and closure of nanosheet” mechanism. During the assembly process, amorphous spherical particles of amphiphilic peptoid oligomers crystallize to form well-defined nanosheets before folding to form single-walled nanotubes. These nanotubes undergo a pH-triggered, reversible contraction–expansion motion. By varying the number of hydrophobic residues of peptoids, we demonstrate tuning of nanotube wall thickness, diameter, and mechanical properties. Atomic force microscopy-based mechanical measurements show peptoid nanotubes are highly stiff (Young’s Modulus ~13–17 GPa). We further demonstrate the precise incorporation of functional groups within nanotubes and their applications in water decontamination and cellular adhesion and uptake. These nanotubes provide a robust platform for developing biomimetic materials tailored to specific applications.
Structural basis of trans-synaptic interactions between PTPδ and SALMs for inducing synapse formation
Authors: Goto-Ito Sakurako , Yamagata Atsushi , Sato Yusuke , Uemura Takeshi , Shiroshima Tomoko , Maeda Asami , Imai Ayako , Mori Hisashi , Yoshida Tomoyuki , Fukai Shuya 
Published: January 2018

AbstractSynapse formation is triggered by trans-synaptic interactions of cell adhesion molecules, termed synaptic organizers. Three members of type-II receptor protein tyrosine phosphatases (classified as type-IIa RPTPs; PTPδ, PTPσ and LAR) are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs) have recently emerged as a family of postsynaptic organizers. Although all five SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly have synaptogenic activities depending on their binding. Here, we report the crystal structures of apo-SALM5, and PTPδ–SALM2 and PTPδ–SALM5 complexes. The leucine-rich repeat (LRR) domains of SALMs interact with the second immunoglobulin-like (Ig) domain of PTPδ, whereas the Ig domains of SALMs interact with both the second and third Ig domains of PTPδ. Unexpectedly, the structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture assay using site-directed SALM5 mutants demonstrates that presynaptic differentiation induced by PTPδ–SALM5 requires the dimeric property of SALM5.
A biosensor-based framework to measure latent proteostasis capacity
Authors: Wood Rebecca J. , Ormsby Angelique R. , Radwan Mona , Cox Dezerae , Sharma Abhishek , Vöpel Tobias , Ebbinghaus Simon , Oliveberg Mikael , Reid Gavin E. , Dickson Alex , Hatters Danny M. 
Published: January 2018

AbstractThe pool of quality control proteins (QC) that maintains protein-folding homeostasis (proteostasis) is dynamic but can become depleted in human disease. A challenge has been in quantitatively defining the depth of the QC pool. With a new biosensor, flow cytometry-based methods and mathematical modeling we measure the QC capacity to act as holdases and suppress biosensor aggregation. The biosensor system comprises a series of barnase kernels with differing folding stability that engage primarily with HSP70 and HSP90 family proteins. Conditions of proteostasis stimulation and stress alter QC holdase activity and aggregation rates. The method reveals the HSP70 chaperone cycle to be rate limited by HSP70 holdase activity under normal conditions, but this is overcome by increasing levels of the BAG1 nucleotide exchange factor to HSPA1A or activation of the heat shock gene cluster by HSF1 overexpression. This scheme opens new paths for biosensors of disease and proteostasis systems.
Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors regardless of gender
Authors: Wei Yi-Chao , Wang Shao-Ran , Jiao Zhuo-Lei , Zhang Wen , Lin Jun-Kai , Li Xing-Yu , Li Shuai-Shuai , Zhang Xin , Xu Xiao-Hong 
Published: January 2018

AbstractThe medial preoptic area (mPOA) differs between males and females in nearly all species examined to date, including humans. Here, using fiber photometry recordings of Ca2+ transients in freely behaving mice, we show ramping activities in the mPOA that precede and correlate with sexually dimorphic display of male-typical mounting and female-typical pup retrieval. Strikingly, optogenetic stimulation of the mPOA elicits similar display of mounting and pup retrieval in both males and females. Furthermore, by means of recording, ablation, optogenetic activation, and inhibition, we show mPOA neurons expressing estrogen receptor alpha (Esr1) are essential for the sexually biased display of these behaviors. Together, these results underscore the shared layout of the brain that can mediate sex-specific behaviors in both male and female mice and provide an important functional frame to decode neural mechanisms governing sexually dimorphic behaviors in the future.
Structured thermal surface for radiative camouflage
Authors: Li Ying , Bai Xue , Yang Tianzhi , Luo Hailu , Qiu Cheng-Wei 
Published: January 2018

AbstractThermal camouflage has been successful in the conductive regime, where thermal metamaterials embedded in a conductive system can manipulate heat conduction inside the bulk. Most reported approaches are background-dependent and not applicable to radiative heat emitted from the surface of the system. A coating with engineered emissivity is one option for radiative camouflage, but only when the background has uniform temperature. Here, we propose a strategy for radiative camouflage of external objects on a given background using a structured thermal surface. The device is non-invasive and restores arbitrary background temperature distributions on its top. For many practical candidates of the background material with similar emissivity as the device, the object can thereby be radiatively concealed without a priori knowledge of the host conductivity and temperature. We expect this strategy to meet the demands of anti-detection and thermal radiation manipulation in complex unknown environments and to inspire developments in phononic and photonic thermotronics.
DNA multi-bit non-volatile memory and bit-shifting operations using addressable electrode arrays and electric field-induced hybridization
Authors: Song Youngjun , Kim Sejung , Heller Michael J. , Huang Xiaohua 
Published: January 2018

AbstractDNA has been employed to either store digital information or to perform parallel molecular computing. Relatively unexplored is the ability to combine DNA-based memory and logical operations in a single platform. Here, we show a DNA tri-level cell non-volatile memory system capable of parallel random-access writing of memory and bit shifting operations. A microchip with an array of individually addressable electrodes was employed to enable random access of the memory cells using electric fields. Three segments on a DNA template molecule were used to encode three data bits. Rapid writing of data bits was enabled by electric field-induced hybridization of fluorescently labeled complementary probes and the data bits were read by fluorescence imaging. We demonstrated the rapid parallel writing and reading of 8 (23) combinations of 3-bit memory data and bit shifting operations by electric field-induced strand displacement. Our system may find potential applications in DNA-based memory and computations.
Superconducting gap anisotropy sensitive to nematic domains in FeSe
Authors: Hashimoto Takahiro , Ota Yuichi , Yamamoto Haruyoshi Q. , Suzuki Yuya , Shimojima Takahiro , Watanabe Shuntaro , Chen Chuangtian , Kasahara Shigeru , Matsuda Yuji , Shibauchi Takasada , Okazaki Kozo , Shin Shik 
Published: January 2018

AbstractThe structure of the superconducting gap in unconventional superconductors holds a key to understand the momentum-dependent pairing interactions. In superconducting FeSe, there have been controversial results reporting nodal and nodeless gap structures, raising a fundamental issue of pairing mechanisms of iron-based superconductivity. Here, by utilizing polarization-dependent laser-excited angle-resolved photoemission spectroscopy, we report a detailed momentum dependence of the gap in single- and multi-domain regions of orthorhombic FeSe crystals. We confirm that the superconducting gap has a twofold in-plane anisotropy, associated with the nematicity due to orbital ordering. In twinned regions, we clearly find finite gap minima near the vertices of the major axis of the elliptical zone-centered Fermi surface, indicating a nodeless state. In contrast, the single-domain gap drops steeply to zero in a narrow angle range, evidencing for nascent nodes. Such unusual node lifting in multi-domain regions can be explained by the nematicity-induced time-reversal symmetry breaking near the twin boundaries.
Novel Miniature Membrane Active Lipopeptidomimetics against Planktonic and Biofilm Embedded Methicillin-Resistant Staphylococcus aureus
Authors: Joshi Seema , Mumtaz Sana , Singh Jyotsna , Pasha Santosh , Mukhopadhyay Kasturi 
Published: January 2018

AbstractEscalating multidrug resistance and highly evolved virulence mechanisms have aggravated the clinical menace of methicillin-resistant Staphylococcus aureus (MRSA) infections. Towards development of economically viable staphylocidal agents here we report eight structurally novel tryptophan-arginine template based peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S-7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and good to potent activity against clinically relevant pathogens MRSA, methicillin-resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus faecium (MIC: 1.4–22.7 μg/mL). Mechanistically, the active peptidomimetics dissipated membrane potential and caused massive permeabilization on MRSA concomitant with loss of viability. Against stationary phase MRSA under nutrient-depleted conditions, active peptidomimetics S-7 and S-8 achieved > 6 log reduction in viability upon 24 h incubation while both S-7 (at 226 μg/mL) and S-8 (at 28 μg/mL) also destroyed 48 h mature MRSA biofilm causing significant decrease in viability (p < 0.05). Encouragingly, most active peptidomimetic S-8 maintained efficacy against MRSA in presence of serum/plasma while exhibiting no increase in MIC over 17 serial passages at sub-MIC concentrations implying resistance development to be less likely. Therefore, we envisage that the current template warrants further optimization towards the development of cell selective peptidomimetics for the treatment of device associated MRSA infections.