bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capturing the Differences between Humoral Immunity in the Normal and Tumor Environments from Repertoire-Seq of B-Cell Receptors Using Supervised Machine Learning
Authors: Konishi Hiroki , Komura Daisuke , Katoh Hiroto , Atsumi Shinichiro , Koda Hirotomo , Yamamoto Asami , Seto Yasuyuki , Massashi Fukayama , Yamaguchi Rui , Imoto Seiya , Ishikawa Shumpei 
Published: September 2017

ABSTRACTThe recent success of immunotherapy in treating tumors has attracted increasing interest in research related to the adaptive immune system in the tumor microenvironment. Recent advances in next-generation sequencing technology enabled the sequencing of whole T-cell receptors (TCRs) and B-cell receptors (BCRs)/immunoglobulins (Igs) in the tumor microenvironment. Since BCRs/Igs in tumor tissues have high affinities for tumor-specific antigens, the patterns of their amino acid sequences and other sequence-independent features such as the number of somatic hypermutations (SHMs) may differ between the normal and tumor microenvironments. However, given the high diversity of BCRs/Igs and the rarity of recurrent sequences among individuals, it is far more difficult to capture such differences in BCR/Ig sequences than in TCR sequences. The aim of this study was to explore the possibility of discriminating BCRs/Igs in tumor and in normal tissues, by capturing these differences using supervised machine learning methods applied to RNA sequences of BCRs/Igs.RNA sequences of BCRs/Igs were obtained from matched normal and tumor specimens from 90 gastric cancer patients. BCR/Ig-features obtained in Rep-Seq were used to classify individual BCR/Ig sequences into normal or tumor classes. Different machine learning models using various features were constructed as well as gradient boosting machine (GBM) classifier combining these models. The results demonstrated that BCR/Ig sequences between normal and tumor microenvironments exhibit their differences. Next, by using a GBM trained to classify individual BCR/Ig sequences, we tried to classify sets of BCR/Ig sequences into normal or tumor classes. As a result, an area under the curve (AUC) value of 0.826 was achieved, suggesting that BCR/Ig repertoires have distinct sequence-level features in normal and tumor tissues.To the best of our knowledge, this is the first study to show that BCR/Ig sequences derived from tumor and normal tissues have globally distinct patterns, and that these tissues can be effectively differentiated using BCR/Ig repertoires.
Internal amino acid state modulates yeast taste neurons to support protein homeostasis inDrosophila
Authors: Steck Kathrin , Walker Samuel J. , Itskov Pavel M. , Baltazar Célia , Ribeiro Carlos 
Published: September 2017

ABSTRACTTo optimize fitness, animals must dynamically match food choices to their current needs. For drosophilids, yeast fulfils most dietary protein and micronutrient requirements. While several yeast metabolites activate known gustatory receptor neurons (GRNs) inDrosophila melanogaster, the chemosensory channels mediating yeast feeding remain unknown. Here we identify a class of proboscis GRNs required for yeast intake, and show that these GRNs act redundantly to mediate yeast feeding. While nutritional and reproductive states synergistically increase yeast appetite, we find a separation of these state signals at the level of GRN responses to yeast: amino acid but not mating state enhances yeast GRN gain. The sensitivity of sweet GRNs to sugar is not increased by protein deprivation, providing a potential basis for protein-specific appetite. The emerging picture is that different internal states act at distinct levels of a dedicated gustatory circuit to elicit nutrient-specific appetites towards a complex, ecologically relevant protein source.
An automated high-throughput system for phenotypic screening of chemical libraries onC. elegansand parasitic nematodes
Authors: Partridge Frederick A. , Brown Anwen E. , Buckingham Steven D. , Willis Nicky J. , Wynne Graham M. , Forman Ruth , Else Kathryn J. , Morrison Alison A. , Matthews Jacqueline B. , Russell Angela J. , Lomas David A. , Sattelle David B. 
Published: September 2017

AbstractParasitic nematodes infect hundreds of millions of people and farmed livestock. Further, plant parasitic nematodes result in major crop damage. The pipeline of therapeutic compounds is limited and parasite resistance to the existing anthelmintic compounds is a global threat. We have developed an INVertebrate Automated Phenotyping Platform (INVAPP) for high-throughput, plate-based chemical screening, and an algorithm (Paragon) which allows screening for compounds that have an effect on motility and development of parasitic worms. We have validated its utility by determining the efficacy of a panel of known anthelmintics against model and parasitic nematodes:Caenorhabditis elegans, Haemonchus contortus, Teladorsagia circumcincta, andTrichuris muris. We then applied the system to screen the Pathogen Box chemical library in a blinded fashion and identified known anthelmintics, including tolfenpyrad, auranofin, and mebendazole and 14 compounds previously undescribed as anthelmintics, including benzoxaborole and isoxazole chemotypes. This system offers an effective, high-throughput system for the discovery of novel anthelmintics.
Real-time fluorescence and deformability cytometry — flow cytometry goes mechanics
Authors: Rosendahl Philipp , Plak Katarzyna , Jacobi Angela , Kraeter Martin , Toepfner Nicole , Otto Oliver , Herold Christoph , Winzi Maria , Herbig Maik , Ge Yan , Girardo Salvatore , Wagner Katrin , Baum Buzz , Guck Jochen 
Published: September 2017

AbstractCell mechanical characterization has recently approached the throughput of conventional flow cytometers. However, this very sensitive, label-free approach still lacks the specificity of molecular markers. Here we combine real-time 1D-imaging fluorescence and deformability cytometry (RT-FDC) to merge the two worlds in one instrument — opening many new research avenues. We demonstrate its utility using sub-cellular fluorescence localization to identify mitotic cells and test for their mechanical changes in an RNAi screen.
Issues of quality and professionalism of library volunteers
Authors: Casselden Biddy , Walton Geoff , Pickard Alison , Mcleod Julie 
Published: September 2017

Purpose
The purpose of this paper is to consider the preliminary findings arising from two case study library authorities in the North East of England, examining current volunteer use in Public Libraries. Specific reference to quality and professionalism will be discussed, to identify key trends and ways forward.

Design/methodology/approach
This research involved a series of interviews with key staff, a staff survey, user survey and volunteer focus groups.

Findings
The early-stage results of the qualitative analysis are reported, including key emergent themes relating to quality and professionalism. Triangulation of the key stakeholder opinions will be carried out.

Research limitations/implications
This research relates to an area that is a key factor of modern public library provision, and helps to illustrate the complex environment that exists.

Practical implications
Volunteer use in public libraries is a feature of the hybrid model of library provision in the twenty-first century, and the need to ensure quality and professionalism to improve service provision is even more critical.

Social implications
This research considers current thinking amongst stakeholders within public libraries and attempts to move the debate about volunteer use in library service provision forward.

Originality/value
It provides initial thoughts on what features are essential for successful volunteer use in public libraries, with regard to quality and professionalism.
Stop chasing unicorns
Authors: Gariepy Laura W. , Peacemaker Bettina , Colon Valeriana 
Published: September 2017

Purpose
The purpose of this paper is to discuss the importance of selecting “well-matched” independent and dependent variables in quantitative research to maximize the possibility of detecting impact of library services on indicators of student success. The paper introduces the concept of sensitivity, which is the extent to which a measure will detect change in the thing being measured.

Design/methodology/approach
To make the case, the authors use the impact of amount of library instruction received on Grade Point Average (GPA) as an example, explaining a correlational research study at their institution. However, the emphasis of the paper is on the conceptual importance of sensitivity in variable selection in quantitative studies of all types.

Findings
After finding no statistically significant relationship between the amount of library instruction received and GPA, the authors determined that GPA was not a sensitive enough variable to detect the impact of a few class sessions taught by a librarian throughout students entire undergraduate career. Based on the findings and the literature, the authors conclude that the practice of selecting “insensitive” dependent variables that are unlikely to detect impact of the independent variable is a common practice in the library assessment literature.

Originality/value
In an era where bigger is better when it comes to demonstrating impact of library services, this paper argues that libraries sometimes diminish their ability to illustrate their contributions to student success by choosing large scale indicators of student success as independent variables which fail to detect the impact of library services.
Characterization of the functional activity of botulinum neurotoxin subtype B6
Authors: Kohda Tomoko , Nakamura Keiji , Hosomi Koji , Torii Yasushi , Kozaki Shunji , Mukamoto Masafumi 
Published: September 2017

ABSTRACTClostridium botulinum produces the highly potent neurotoxin, botulinum neurotoxin (BoNT), which is classified into seven serotypes (A–G); the subtype classification is confirmed by the diversity of amino acid sequences among the serotypes. BoNT from the Osaka05 strain is associated with type B infant botulism and has been classified as BoNT/B subtype B6 (BoNT/B6) by phylogenetic analysis and the antigenicity of its C‐terminal heavy chain (HC) domain. However, the molecular bases for its properties, including its potency, are poorly understood. In this study, BoNT/B6 holotoxin was purified and the biological activity and receptor binding activity of BoNT/B6 compared with those of the previously‐characterized BoNT/B1 and BoNT/B2 subtypes. The derivative BoNT/B6 was found to be already nicked and in an activated form, indicating that endogenous protease production may be higher in this strain than in the other two strains. BoNT/B1 exhibited the greatest lethal activity in mice, followed by BoNT/B6, which is consistent with the sensitivity of PC12 cells. No significant differences were seen in the enzymatic activities of the BoNT/Bs against their substrate. HC/B1 and HC/B6 exhibited similar binding affinities to synaptotagmin II (SytII), which is a specific protein receptor for BoNT/B. Binding to the SytII/ganglioside complex is functionally related to the toxic action; however, the receptor recognition sites are conserved. These results suggest that the distinct characteristics and differences in biological sensitivity of BoNT/B6 may be attributable to the function of its Hc.domain.
Comparing Generic Drug Markets in Europe and the United States: Prices, Volumes, and Spending
Authors: WOUTERS OLIVIER J. , KANAVOS PANOS G. , McKEE MARTIN 
Published: September 2017

Policy Points:
Our study indicates that there are opportunities for cost savings in generic drug markets in Europe and the United States.
Regulators should make it easier for generic drugs to reach the market.
Regulators and payers should apply measures to stimulate price competition among generic drugmakers and to increase generic drug use.
To meaningfully evaluate policy options, it is important to analyze historical context and understand why similar initiatives failed previously.
ContextRising drug prices are putting pressure on health care budgets. Policymakers are assessing how they can save money through generic drugs.MethodsWe compared generic drug prices and market shares in 13 European countries, using data from 2013, to assess the amount of variation that exists between countries. To place these results in context, we reviewed evidence from recent studies on the prices and use of generics in Europe and the United States. We also surveyed peer‐reviewed studies, gray literature, and books published since 2000 to (1) outline existing generic drug policies in European countries and the United States; (2) identify ways to increase generic drug use and to promote price competition among generic drug companies; and (3) explore barriers to implementing reform of generic drug policies, using a historical example from the United States as a case study.FindingsThe prices and market shares of generics vary widely across Europe. For example, prices charged by manufacturers in Switzerland are, on average, more than 2.5 times those in Germany and more than 6 times those in the United Kingdom, based on the results of a commonly used price index. The proportion of prescriptions filled with generics ranges from 17% in Switzerland to 83% in the United Kingdom. By comparison, the United States has historically had low generic drug prices and high rates of generic drug use (84% in 2013), but has in recent years experienced sharp price increases for some off‐patent products. There are policy solutions to address issues in Europe and the United States, such as streamlining the generic drug approval process and requiring generic prescribing and substitution where such policies are not yet in place. The history of substitution laws in the United States provides insights into the economic, political, and cultural issues influencing the adoption of generic drug policies.ConclusionsGovernments should apply coherent supply‐ and demand‐side policies in generic drug markets. An immediate priority is to convince more physicians, pharmacists, and patients that generic drugs are bioequivalent to branded products. Special‐interest groups continue to obstruct reform in Europe and the United States.
Transitional justice as social control: political transitions, human rights norms and the reclassification of the past
Authors: Dudai Ron 
Published: September 2017

AbstractThis article offers an interpretation of transitional justice policies – the efforts of post‐conflict and post‐dictatorship societies to address the legacy of past abuses – as a form of social control. While transitional justice is commonly conceptualized as responding to a core problem of impunity, this article argues that such formulation is too narrow and leads to lack of coherence in the analysis of the diverse array of transitional mechanisms, which include among others trials, truth commissions, reparations for victims and apologies. Building on the work of Stanley Cohen, the article contends that the core transitional problem is the denial of human rights violations, and consequently that the common purpose of all transitional justice mechanisms is to reclassify the past: redefining as deviant some acts and individuals which prior to the transition were considered ‘normal’. The article identifies and analyses three themes in the application of a social control framework to transitional justice: (1)truth, memory and retroactive social control, pertains to the way truth‐seeking transitional justice mechanisms reclassify past events by engaging in social control of and through memory; (2)censure, celebration and transitional social controlrefers to the reclassification of categories of individuals through expressions of both social disapproval and praise; and (3)civil society and social control from belowconcerns the role of social movements, organizations and groups as informal agents of social control during transitions. The concluding section recaps and briefly explores the concept of ‘good moral panic’ in the context of political transitions. While the concept of social control tends to have negative connotations for critical sociologists, this work suggests that efforts to categorize, punish and disapprove certain behaviours as deviant may not only be viewed as supporting a conservative status‐quo, but also as promoting fledging human rights norms.
State‐of‐the‐Art Chocolate Manufacture: A Review
Authors: Gutiérrez Tomy J. 
Published: September 2017

AbstractThe aroma, taste, shine, snap, smoothness, “melt‐in‐your‐mouth” sensation, and texture are all qualities that define chocolate, and all depend on how the cocoa and the chocolate itself are processed. Postharvest handling of the cocoa (fermentation, drying, cleaning, storage, and transport) and its transformation into chocolate (roasting, grinding, conching, tempering, molding, and the addition of core and other ingredients), as well as the packaging, storage, transport, and refrigeration of the finished product all have an important influence on the characteristics of chocolate. The aim of this review was to identify and study the key factors, including microbiological aspects that affect the quality of chocolate, from harvesting the beans right up to the manufacture of the finished products.
Shiga‐toxin Producing Escherichia coli: Pathogenicity, Supershedding, Diagnostic Methods, Occurrence, and Foodborne Outbreaks
Authors: Castro Vinicius Silva , Carvalho Ricardo César Tavares , Conte‐Junior Carlos Adam , Figuiredo Eduardo Eustáquio Souza 
Published: September 2017

AbstractHistorically, Escherichia coli is among the most studied organisms and serves as the basis for understanding many fundamental biochemical and genetic concepts. In addition, it displays 9 pathogenesis groups, with the Shiga toxin‐producing (STEC) group being the main representative regarding foodborne pathogenesis. Its typical characteristic is the presence of 2 distinct toxins and variants: stx1 (stx1a, stx1c, and stx1d), and stx2 (stx2a, stx2b, stx2c, stx2d, stx2e, stx2f, and stx2g). The main challenge regarding the study of E. coli is the standardization of a high sensitivity method including all pathotypes, that allows for enrichment of STEC cells and a decrease of background microbiota. The ability of some E. coli cells belonging to other pathogenic groups, such as O104:H4, to acquire genes unique to the STEC group, increases the pathogenic power and the risk of new outbreaks related to these bacteria. In addition, animals with a high concentration of pathogenic E. coli cells present in feces (above 104 CFU/g), designated as supershedding animals, may be the primary transmission factor among ruminants. Therefore, the purpose of this review is to address pathogenicity factors and the importance of supershedding animals in the transmission of this pathogen, discussing the main methods currently applied, to focus on the occurrence of STEC in beef.
Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers
Authors: Li Xingbao , Sahlem Gregory L. , Badran Bashar W. , McTeague Lisa M. , Hanlon Colleen A. , Hartwell Karen. J. , Henderson Scott , George Mark S. 
Published: September 2017

Background and ObjectiveSeveral studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue‐elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub‐cortical neural activity in non‐treatment seeking nicotine‐dependent participants.MethodsWe conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s‐on, 10 s‐off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session.ResultsA total of 11 non‐treatment seeking nicotine‐dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS.ConclusionsThis preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers.Scientific SignificancerTMS may exert its anti‐craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788–794)
Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force
Authors: Miskowiak KW , Burdick KE , Martinez‐Aran A , Bonnin CM , Bowie CR , Carvalho AF , Gallagher P , Lafer B , López‐Jaramillo C , Sumiyoshi T , McIntyre RS , Schaffer A , Porter RJ , Torres IJ , Yatham LN , Young AH , Kessing LV , Vieta E 
Published: September 2017

AbstractObjectivesTo aid the development of treatment for cognitive impairment in bipolar disorder, the International Society for Bipolar Disorders (ISBD) convened a task force to create a consensus‐based guidance paper for the methodology and design of cognition trials in bipolar disorder.MethodsThe task force was launched in September 2016, consisting of 18 international experts from nine countries. A series of methodological issues were identified based on literature review and expert opinion. The issues were discussed and expanded upon in an initial face‐to‐face meeting, telephone conference call and email exchanges. Based upon these exchanges, recommendations were achieved.ResultsKey methodological challenges are: lack of consensus on how to screen for entry into cognitive treatment trials, define cognitive impairment, track efficacy, assess functional implications, and manage mood symptoms and concomitant medication. Task force recommendations are to: (i) enrich trials with objectively measured cognitively impaired patients; (ii) generally select a broad cognitive composite score as the primary outcome and a functional measure as a key secondary outcome; and (iii) include remitted or partly remitted patients. It is strongly encouraged that trials exclude patients with current substance or alcohol use disorders, neurological disease or unstable medical illness, and keep non‐study medications stable. Additional methodological considerations include neuroimaging assessments, targeting of treatments to illness stage and using a multimodal approach.ConclusionsThis ISBD task force guidance paper provides the first consensus‐based recommendations for cognition trials in bipolar disorder. Adherence to these recommendations will likely improve the sensitivity in detecting treatment efficacy in future trials and increase comparability between studies.