bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐blocks are suitable material for programmed cell death ligand‐1 immunohistochemistry: Comparison of cell‐blocks and matched surgical resection specimens in lung cancer
Authors: Pak Min Gyoung , Roh Mee Sook 
Published: June 2019

AbstractObjectiveProgrammed cell death ligand‐1 (PD‐L1) has emerged as a predictive biomarker in lung cancer. PD‐L1 immunohistochemistry (IHC) assay predicts the response to immunotherapy, but cytology specimens are often the only samples available in a considerable proportion of advanced lung cancer patients. We delineate practical feasibility and efficacy of cytology cell‐block (CB) specimens for PD‐L1 expression and concordance between cytology CBs and surgical resection specimens.MethodsIn total, 58 eligible patients with primary lung cancer who received computed tomography‐guided percutaneous needle aspiration and surgery were included. PD‐L1 IHC (clone SP263) was performed on CBs prepared from residual liquid‐based cytology material and matched surgical resection specimens. PD‐L1 positive tumour cell proportion was categorised in four score groups: (a) <1%; (b) ≤1% to <10%; (c) ≤10% to <50%, (d) ≥50%.ResultsComparison of PD‐L1 expression in cytology CBs and matched surgical resection specimens showed a high concordance (κ value 0.65). According to the therapeutic guideline of immunotherapeutic agents, a positive percent agreement was 94.34%, and a negative percent agreement was 100% at a cut‐off value for positivity of 1% PD‐L1 expression. There was a significant difference observed with regard to rates of PD‐L1 positivity when comparing smoking history (P = 0.02), age (P = 0.04) and pathological TNM stage (P = 0.04).ConclusionsThe results show that cytology CBs evaluated for PD‐L1 IHC assay have high concordance with matched surgical resection specimens and can be used for assessing PD‐L1 expression. Also, we propose that CBs are suitable materials for evaluating PD‐L1 expression while simultaneously performing both diagnostic and molecular tests.
Harmless? A hierarchical analysis of poppers use correlates among young gay and bisexual men
Authors: Demant Daniel , Oviedo‐Trespalacios Oscar 
Published: June 2019

AbstractIntroduction and AimsPoppers (alkyl nitrites) are recreational substances commonly used during sexual activity. The current legal status of poppers is complex and wide‐ranging bans are increasingly under discussion. Research has identified disproportionate levels of poppers use in sexual minority men. While research on poppers use among sexual minority men exists, little is known about poppers use patterns and correlations with psychosocial and other factors among gay and bisexual young men.Design and MethodsA cross‐sectional survey was conducted with 836 Australian gay and bisexual young men aged 18 to 35 years. Descriptive statistics and hierarchical segmentation analyses were conducted to identify poppers use patterns, and correlates of recent poppers use (past 3 months) with personal characteristics, use of other substances, as well as mental and psychosocial health including minority stress, LGBT‐community connectedness and participation.ResultsHigh levels of lifetime (38%, n = 315) and recent (24%, n = 204) poppers use were reported. However, few participants reported dependency symptoms, risky consumption or problems arising from using poppers. The final model included three variables (visiting sex‐on‐premises venues, licensed LGBT venues, and using other substances) and predicted 85% (n = 174) of recent poppers use. No correlations with other concepts or characteristics could be identified.ConclusionThis analysis further supports the hypothesis that poppers may be substances with a comparably low‐risk profile. A regulation of poppers with a harm reduction approach may present a valuable public health intervention.
Evolution of nodal and nodal‐related genes and the putative composition of the heterodimers that trigger the nodal pathway in vertebrates
Authors: Opazo Juan C. , Kuraku Shigehiro , Zavala Kattina , Toloza‐Villalobos Jessica , Hoffmann Federico G. 
Published: June 2019

AbstractNodal is a signaling molecule that belongs to the transforming growth factor‐β superfamily that plays key roles during the early stages of development of animals. In vertebrates Nodal forms an heterodimer with a GDF1/3 protein to activate the Nodal pathway. Vertebrates have a paralog of nodal in their genomes labeled Nodal‐related, but the evolutionary history of these genes is a matter of debate, mainly because of the presence of a variable numbers of genes in the vertebrate genomes sequenced so far. Thus, the goal of this study was to investigate the evolutionary history of the Nodal and Nodal‐related genes with an emphasis in tracking changes in the number of genes among vertebrates. Our results show the presence of two gene lineages (Nodal and Nodal‐related) that can be traced back to the ancestor of jawed vertebrates. These lineages have undergone processes of differential retention and lineage‐specific expansions. Our results imply that Nodal and Nodal‐related duplicated at the latest in the ancestor of gnathostomes, and they still retain a significant level of functional redundancy. By comparing the evolution of the Nodal/Nodal‐related with GDF1/3 gene family, it is possible to infer that there are several types of heterodimers that can trigger the Nodal pathway among vertebrates.
Retracted: Bevacizumab synergises with the BCL 2 inhibitor venetoclax to effectively treat B‐cell non‐Hodgkin's lymphoma
Authors: Wang Li , Peng Shaoyong , Sun Weipeng , Liu Xiaoxia 
Published: June 2019

AbstractObjectivesOur present study has shown a potential role for VEGF‐A‐mediated autocrine signalling to promote survival and proliferation of SU‐DHL‐6 cells, but the cells could not undergo apoptosis but rather decrease proliferation after bevacizumab treatment. Therefore, we would like to further study the antitumour efficacy of venetoclax (BCL2 inhibitor) in combination with bevacizumab in B‐cell NHL.MethodsThe human cytokine antibody array, RT‐qPCR, Western blot, ELISA, apoptosis assay and xenografted mouse model et al were used.ResultsWe described a unique phenomenon that SU‐DHL‐6 cells showed cell density‐dependent survival and growth. Then, we suggested the expression of VEGF‐A was positively correlated with the cell density using a human cytokine antibody array and indicated an important role of VEGF‐A in the survival and proliferation of SU‐DHL‐6 cells. Additionally, xenografted SU‐DHL‐6 cells formed tumours in mice that grew in response to VEGF stimulation. GEO data set also suggested that high VEGF‐A expression reflected poor prognosis. The combination therapy with bevacizumab and navitoclax could significantly induce of cell death in vitro and reduce the tumour size and weight with well tolerated in vivo.ConclusionsOur findings propose a novel combined strategy in which bevacizumab synergises with the BCL2 inhibitor venetoclax that is effective against B‐cell NHL.
Spatiotemporal expression pattern of PERIOD 1 and PERIOD 2 in the mouse SCN is dependent on VIP receptor 2 signaling
Authors: Hannibal Jens , Norn Tania H. B. , Georg Birgitte , Fahrenkrug Jan 
Published: June 2019

AbstractNeurons of the hypothalamic suprachiasmatic nucleus (SCN) express clock genes, which regulate their own transcription and generate daily output signals driving circadian rhythmic behavior and physiology. The neuropeptide VIP and its specific receptor, the VPAC2 receptor, are important for synchronization of clock neurons. In the present study, we characterized PER1 and PER2 expressing neurons in wild‐type and VPAC2‐deficient mice. We found evidence for distinct spatiotemporal circadian oscillation in the expression of the PER genes in two separate clusters of SCN neurons. In wild‐type mice corresponding to the SCN shell and ventral core, high expression of PER was found at lights‐off most likely representing an evening clock (E‐clock). In another smaller cluster of neurons located in the central core of the SCN, PER expression peaks in antiphase at lights‐on and could represent a morning clock (M‐clock). BMAL1 immunoreactivity was found to be expressed in antiphase to PER in M and E neurons, respectively. PER was found in 98% of neurons expressing vasopressin (AVP) and in 92% of VIP neurons. The chemotype of M neurons was not identified. M but not E cells were responsive to long but not short photoperiods. The expression of the VPAC2 receptor was found in both M and E cells, and VPAC2‐deficient mice displayed markedly blunted PER expression in both cell clusters of the SCN. Conclusion: These observations support the existence of M and E clocks involved in circadian and seasonal adaptation, which seem dependent on intact VIP/VPAC2 signaling in the SCN.
What single‐unit recording studies tell us about the basic mechanisms of sleep and wakefulness
Authors: Sakai Kazuya 
Published: June 2019

AbstractThis paper reviews the presence, localization and characteristics of state‐specific neurons in the mouse forebrain, midbrain and hindbrain that are involved in the control of ultradian sleep–wake cycles and shows that all these regions contain basic neural elements capable of generating the sleep–wake cycle. The chronic single‐unit recording method in unanaesthetized animals is useful for unravelling the dynamics of sleep–wake switching, in particular because it can analyse events at the level of single neurons, thereby decoding information used by the brain in determining its functional state. A prerequisite is to record a large number of all types of neurons, identify critical wake‐ and sleep‐promoting neurons and determine their activity profiles during the sleep–wake cycle and their trends in spike activity during the state transitions from wakefulness to sleep and from sleep to wakefulness in the same species. Here, I argue that single‐unit recordings in unanaesthetized mice help us to (a) determine key neural elements controlling sleep–wake dynamics, (b) elucidate the roles of forebrain and brainstem neurons in ultradian sleep–wake cyclicity and (c) gain a new insight into the functional significance of wakefulness, slow‐wave sleep and paradoxical (or rapid eye movement) sleep. I also discuss the merits and limitations of single‐unit recording compared with more recent genetic approaches, and I suggest that findings from studies using the classic electrophysiological technique will provide the foundation for future studies using new genetic techniques to dissect the neural networks responsible for the initiation, maintenance and cessation of each wake and sleep state.
When words hurt: Verbal suggestion prevails over conditioning in inducing the motor nocebo effect
Authors: Corsi Nicole , Emadi Andani Mehran , Sometti Davide , Tinazzi Michele , Fiorio Mirta 
Published: June 2019

AbstractPerception and behavior are strongly influenced by the verbal information conveyed by other individuals (e.g., verbal suggestion) and by learning (e.g., conditioning). This influence is well represented by the placebo and nocebo effects, in which positive verbal suggestion associated with positive conditioning induces beneficial outcomes (placebo effect), while the opposite is true for the negative counterpart (nocebo effect). It is still unclear whether verbal suggestion and conditioning exert distinctive roles in influencing perception, behavior and motor system activity when they occur in opposite directions. To this purpose, fifty‐three healthy volunteers were assigned to four groups characterized by either congruent or incongruent verbal suggestion and conditioning. Participants were asked to perform a force motor task by pressing a piston as strongly as possible. Transcranial magnetic stimulation over the primary motor cortex was used to record motor evoked potentials (MEP) and cortical silent period (CSP) from the muscle involved in the task. We found that negative verbal suggestion counteracted positive conditioning and induced sense of weakness, effort, and force decrements. MEP amplitude was stable, whereas the CSP duration shortened in all the groups throughout the procedure, indicating the involvement of cortical inhibitory circuits, independently of the type of verbal suggestion or conditioning. Our findings highlight a prevalent role of verbal suggestion over conditioning in determining a worsening (nocebo effect) but not an improvement (placebo effect) of motor performance. These results suggest that words associated with treatments should be chosen carefully to avoid negative outcomes, especially in sports and clinical settings.
Deficiency, Contamination, and the Signal Processing Metaphor
Authors: Newton Paul E. 
Published: June 2019

AbstractEducational assessment involves eliciting, transmitting, and receiving information concerning the level of proficiency of a learner in a specified domain. With that in mind, it is perhaps surprising that the literature seems to make very little use of the signal processing metaphor. The present article begins by making a general case for greater use of this metaphor, as a simple and intuitive thinking tool for helping to explain how educational assessment works. The main body of the article extends this argument by demonstrating the utility of the metaphor in helping to explain how educational assessment can go wrong. During the 1980s and 1990s, Samuel Messick extensively discussed two major ways in which educational assessment can go wrong via construct‐irrelevant variance and construct underrepresentation, respectively. Despite their importance, these concepts have had only a limited impact on the literature. Part of the reason for this may be a lack of clarity and comprehensiveness in their articulation. The present article aims to articulate these concepts more clearly and comprehensively, within a framework provided by the signal processing metaphor, reconfiguring them as signal contamination and signal deficiency, respectively.
Sulfasalazine decreases mouse cortical hyperexcitability
Authors: Alcoreza Oscar , Tewari Bhanu P. , Bouslog Allison , Savoia Andrew , Sontheimer Harald , Campbell Susan L. 
Published: June 2019

AbstractObjectiveCurrently prescribed antiepileptic drugs (AEDs) are ineffective in treating approximately 30% of epilepsy patients. Sulfasalazine (SAS) is an US Food and Drug Administration (FDA)–approved drug for the treatment of Crohn disease that has been shown to inhibit the cystine/glutamate antiporter system xc‐ (SXC) and decrease tumor‐associated seizures. This study evaluates the effect of SAS on distinct pharmacologically induced network excitability and determines whether it can further decrease hyperexcitability when administered with currently prescribed AEDs.MethodsUsing in vitro cortical mouse brain slices, whole‐cell patch‐clamp recordings were made from layer 2/3 pyramidal neurons. Epileptiform activity was induced with bicuculline (bic), 4‐aminopyridine (4‐AP) and magnesium‐free (Mg2+‐free) solution to determine the effect of SAS on epileptiform events. In addition, voltage‐sensitive dye (VSD) recordings were performed to characterize the effect of SAS on the spatiotemporal spread of hyperexcitable network activity and compared to currently prescribed AEDs.ResultsSAS decreased evoked excitatory postsynaptic currents (eEPSCs) and increased the decay kinetics of evoked inhibitory postsynaptic currents (eIPSCs) in layer 2/3 pyramidal neurons. Although application of SAS to bic and Mg2+‐free–induced epileptiform activity caused a decrease in the duration of epileptiform events, SAS completely blocked 4‐AP–induced epileptiform events. In VSD recordings, SAS decreased VSD optical signals induced by 4‐AP. Co‐application of SAS with the AED topiramate (TPM) caused a significantly further decrease in the spatiotemporal spread of VSD optical signals.SignificanceTaken together this study provides evidence that inhibition of SXC by SAS can decrease network hyperexcitability induced by three distinct pharmacologic agents in the superficial layers of the cortex. Furthermore, SAS provided additional suppression of 4‐AP–induced network activity when administered with the currently prescribed AED TPM. These findings may serve as a foundation to assess the potential for SAS or other compounds that selectively target SXC as an adjuvant treatment for epilepsy.
Advancing research toward faster diagnosis, better treatment, and end of stigma in epilepsy
Authors: Pitkänen Asla , Henshall David C. , Cross J. Helen , Guerrini Renzo , Jozwiak Sergiusz , Kokaia Merab , Simonato Michele , Sisodiya Sanjay , Mifsud Janet 
Published: June 2019

AbstractSeven large European Union (EU)–funded epilepsy‐related research projects joined forces in May 2018 in Brussels, Belgium, in a unique community building event—the epiXchange conference. During this conference, 170 investigators from the projects DESIRE, EpimiRNA, EPISTOP, EpiTarget, EpiXchange, and EpiPGX as well as the European Reference Network EpiCARE, met up with key stakeholders including representatives of the European Commission, patient organizations, commercial partners, and other European and International groups. The epiXchange conference focused on sharing and reviewing the advances made by each project in the previous 5 years; describing the infrastructures generated; and discussing the innovations and commercial applications across five thematic areas: biomarkers, genetics, therapeutics, comorbidities, and biobanks and resources. These projects have, in fact, generated major breakthroughs including the discovery of biofluid‐based molecules for diagnosis, elucidating new genetic causes of epilepsy, creating advanced new models of epilepsy, and the pre‐clinical development of novel compounds. Workshop‐style discussions focused on how to overcome scientific and clinical challenges for accelerating translation of research outcomes and how to increase synergies between the projects and stakeholders at a European level. The resulting advances would lead toward a measurable impact of epilepsy research through better diagnostics, treatments, and quality‐of‐life for persons with epilepsy. In addition, epiXchange provided a unique forum for examining how the different projects could build momentum for future novel groundbreaking epilepsy research in Europe and beyond. This report includes the main recommendations that resulted from these discussions.
Cuckoo and krill herd‐based k‐means++ hybrid algorithms for clustering
Authors: Aggarwal Shruti , Singh Paramvir 
Published: June 2019

AbstractClustering algorithms can be optimized using nature‐inspired techniques. Many algorithms inspired by nature, namely, firefly algorithm, ant colony optimization algorithm, and so forth, have improved clustering results. k‐means is a popular clustering technique but has limitations of local optima, which have been overcome using its various hybrids. k‐means++ is a hybrid k‐means clustering algorithm that gives the procedure to initialize centre of the clusters. In the proposed work, hybrids of nature‐inspired techniques using cuckoo and krill herd algorithm are implemented on k‐means++ algorithm to enhance cluster quality and generate optimized clusters. The designed algorithms are implemented, and the results are compared with their counterparts. Performance parameters such as accuracy, f‐measure, error rate, standard deviation, CPU time, cluster quality check, and so forth are used to measure the clustering capabilities of these algorithms. The results indicate the high performance of newly designed algorithms.
Wearable ECG signal processing for automated cardiac arrhythmia classification using CFASE‐based feature selection
Authors: Zhang Yuwei , Zhang Yuan , Lo Benny , Xu Wenyao 
Published: June 2019

AbstractClassification of electrocardiogram (ECG) signals is obligatory for the automatic diagnosis of cardiovascular disease. With the recent advancement of low‐cost wearable ECG device, it becomes more feasible to utilize ECG for cardiac arrhythmia classification in daily life. In this paper, we propose a lightweight approach to classify five types of cardiac arrhythmia, namely, normal beat (N), atrial premature contraction (A), premature ventricular contraction (V), left bundle branch block beat (L), and right bundle branch block beat (R). The combined method of frequency analysis and Shannon entropy is applied to extract appropriate statistical features. Information gain criterion is employed to select features that the results show that 10 highly effective features can obtain performance measures comparable to those obtained by using the complete features. The selected features are then fed to the input of Random Forest, K‐Nearest Neighbour, and J48 for classification. To evaluate classification performance, tenfold cross validation is used to verify the effectiveness of our method. Experimental results show that Random Forest classifier demonstrates significant performance with the highest sensitivity of 98.1%, the specificity of 99.5%, the precision of 98.1%, and the accuracy of 98.08%, outperforming other representative approaches for automated cardiac arrhythmia classification.
Multistakeholder initiatives in global production networks: naturalizing specific understandings of sustainability through the Better Cotton Initiative
Authors: RIISGAARD LONE , LUND‐THOMSEN PETER , COE NEIL M. 
Published: June 2019

AbstractIn recent years, various academics, consultants, companies and NGOs have advocated a move towards more cooperative approaches to private sustainability standards to address the widely identified shortcomings of the compliance paradigm. However, is it possible to address these limitations by moving towards stakeholder inclusion and capacity building while at the same time catering to the demands of lead firms supplying the mainstream market? In this article, we analyse how the Better Cotton Initiative (BCI) seeks to do just that, in the process identifying three key tensions and competing policy concerns with which standard‐setters have had to grapple – (a) stakeholder inclusion vs process‐control/efficiency; (b) stringency of the standard vs scale of production; and (c) capacity building vs auditing. Combining theoretical considerations about governance in global production networks (GPNs) with a convention theory perspective, we explore these inherent tensions and show that due to pre‐existing power relations in the cotton GPN, it is hard to develop more cooperative approaches because market and industrial values tend to win out despite efforts to follow current best practice on sustainability standard‐setting.
Efficacy and safety of glecaprevir/pibrentasvir as retreatment therapy for patients with genotype 2 chronic hepatitis C who failed prior sofosbuvir plus ribavirin regimen
Authors: Kusakabe Atsunori , Kurosaki Masayuki , Itakura Jun , Joko Kouji , Akahane Takehiro , Tsuji Keiji , Kobashi Haruhiko , Sohda Tetsuro , Kimura Hiroyuki , Narita Ryouichi , Furuta Koichirou , Izumi Namiki 
Published: June 2019

AimRescue therapy for patients with genotype 2 (GT2) chronic hepatitis C who failed prior sofosbuvir (SOF) plus ribavirin (RBV) awaits establishment. This study aims to investigate the efficacy and safety of the fixed‐dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) (GLE/PIB) for patients with GT2 chronic hepatitis C.MethodsIn this nationwide observational study undertaken by the Japanese Red Cross Liver Study Group, 28 GT2 patients with prior failure of SOF + RBV were retreated with GLE/PIB for 12 weeks. We evaluated the rate of sustained virologic response (SVR) and adverse events.ResultsAfter 4 weeks of therapy, serum hepatitis C virus RNA was below the limit of quantification in all patients. The SVR after 4 and 12 weeks of the end of treatment was validated in 100% (28/28) and 100% (28/28), respectively. The adverse events comprised pruritus (eight patients), fatigue (four patients), and appetite loss (four patients), all of which were mild in severity.ConclusionsThis study establishes the efficacy of GLE/PIB as retreatment in Japanese patients with GT2 chronic hepatitis C not responding to SOF + RBV.