bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer
Authors: Feretis Michael , Wang Tengyao , Iype Satheesh , Duckworth Adam , Brais Rebecca , Basu Bristi , Jamieson Neville V. , Huguet Emmanuel , Balakrishnan Anita , Jah Asif , Praseedom Raaj K. , Harper Simon J. , Liau Siong-Seng
Published: September 2017

Objectives

The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival.

Methods

Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1–2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses.

Results

The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables.

Conclusions

Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.
Development of the Aim to Decrease Anxiety and Pain Treatment for Pediatric Functional Abdominal Pain Disorders
Authors: Cunningham Natoshia R. , Nelson Sarah , Jagpal Anjana , Moorman Erin , Farrell Michael , Pentiuk Scott , Kashikar‐Zuck Susmita
Published: September 2017

Objectives:

To evaluate the feasibility and acceptability of the Aim to Decrease Anxiety and Pain Treatment (ADAPT), a brief, on‐line and in‐person behavioral intervention targeting pain and anxiety in youth with functional abdominal pain disorders (FAPDs).

Methods:

Patients were recruited from several outpatient pediatric gastroenterology clinics. Nine participants (ages 9–13) completed the full protocol. Thematic analysis of detailed qualitative feedback was obtained via semistructured patient and caregiver interviews after treatment was conducted. Feasibility and preliminary outcomes were examined using nonparametric tests.

Results:

Preliminary results indicate that the ADAPT treatment is feasible, acceptable, and potentially effective for youth with FAPD. Treatment completers reported that they enjoyed the program and used the skills to manage their pain and worry. Results also indicated that the majority of participants experienced a reduction in anxiety and several reported reductions in pain and functional disability levels.

Conclusions:

Findings from this study suggest that targeting both pain and anxiety may positively impact outcomes in youth with FAPD. The ADAPT intervention has the potential to provide a cost effective and practical application of cognitive behavioral therapy using an innovative combination of in‐person and technology‐based platforms. Overall, the ADAPT intervention is a promising and innovative intervention to improve the outcomes of youth with FAPD.
Nutritional State and Feeding Behaviors of Children With Eosinophilic Esophagitis and Gastroesophageal Reflux Disease
Authors: Mehta Pooja , Furuta Glenn T. , Brennan Taryn , Henry Michelle L. , Maune Nancy Creskoff , Sundaram Shikha S. , Menard‐Katcher Calies , Atkins Dan , Takurukura Faith , Giffen Sandra , Pan Zhaoxing , Haas Angela M.
Published: September 2017

Objective:

As both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) are associated with malnutrition and feeding dysfunction, this study compares growth, nutrition, and feeding behaviors in children with GERD and EoE.

Methods:

Subjects ages 1 to 7 years with GERD or EoE were enrolled in a prospective study. Assessments included length/height, weight, 3‐day food diary, serum biomarkers of nutrition, and the Behavioral Pediatric Feeding Assessment Scale.

Results:

Mean weight‐for‐length z scores in GERD and EoE children were −0.93 and −1.14 (p = NS) and mean body mass index z scores were 0.29 and −0.13 (P = NS). Vitamin D intake was below the daily recommended intake in GERD subjects. EoE subjects’ intake was below daily recommended intake of Vitamin D and calcium. GERD and EoE groups both had normal intake of calories, carbohydrates, proteins, fats, and iron, and normal serum ferritin (25 vs 34 ng/mL), prealbumin (21 vs 20 mg/dL), parathyroid hormone (42 vs 37 pg/mL), and Vitamin D (both 30 ng/mL). Behavioral Pediatric Feeding Assessment Scale problem and frequency scores were similar in GERD and EoE subjects but were higher than those of a historical cohort of healthy controls (Hedges’ g of 0.95 and 1.1, respectively). EoE subjects on food allergen restriction diets had significantly less feeding dysfunction than those on regular diets.

Conclusions:

As a selected group of children with uncomplicated GERD or EoE were without nutritional deficiencies but had maladaptive feeding, providing anticipatory guidance to minimize mealtime challenges, monitoring for improvement, or referring to a feeding therapist, may be beneficial. A trial of food allergen restriction may provide additional benefit for those with EoE.
HIV Preexposure Prophylaxis Implementation at Local Health Departments: A Statewide Assessment of Activities and Barriers
Authors: Zhang Helen L. , Rhea Sarah K. , Hurt Christopher B. , Mobley Victoria L. , Swygard Heidi , Seña Arlene C. , McKellar Mehri S.
Published: September 2017

Background:

Expanding access to HIV preexposure prophylaxis (PrEP) could help reduce rates of HIV infection in the United States. This study characterizes activities and barriers to PrEP implementation at local health departments (LHDs) in North Carolina (NC), which contains a large rural population.

Methods:

In May 2016, a web-based survey was distributed to health directors of all county and district health departments in NC to assess PrEP-related activities, perceived barriers to PrEP implementation, and desired PrEP-related resources.

Results:

Of 85 LHDs in NC, 56 (66%) responded to the survey. Of these, 2 (4%) reported PrEP prescribing and 7 (13%) externally referred for PrEP services. Among the 54 departments not prescribing PrEP, the most frequently cited reasons were cost concerns (n = 25, 46%), lack of formal prescribing protocols (n = 21, 39%), and belief that PrEP would be better managed at primary care or specialty clinics (n = 19, 35%). Among the 47 departments not prescribing or referring clients for PrEP, the most frequently cited reasons for the lack of PrEP referral were the absence of local PrEP providers (n = 29, 62%), lack of PrEP knowledge among staff (n = 13, 28%), and perceived lack of PrEP candidates (n = 12, 26%). The most frequently requested PrEP-related resources included training to help identify PrEP candidates (n = 39, 70%) and training on PrEP prescribing and management (n = 38, 68%).

Conclusions:

PrEP prescribing and referral among LHDs in NC remains extremely limited. Increased PrEP-related training and support for LHD-based providers could enhance PrEP access, especially in rural and underserved areas.
Multiparametric Magnetic Resonance Imaging of Prostate Cancer Bone Disease
Authors: Perez-Lopez Raquel , Nava Rodrigues Daniel , Figueiredo Ines , Mateo Joaquin , Collins David J. , Koh Dow-Mu , de Bono Johann S. , Tunariu Nina
Published: September 2017

Objectives

The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases.

Materials and Methods

Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations. Univariate and multivariate logistic regression models were analyzed.

Results

Median ADC and nDWI signal was significantly higher, and median swFF was significantly lower, in bone metastases than nonmetastatic bone (P < 0.001). In the metastatic cohort, 31 (72.1%) of 43 biopsies had detectable cancer cells. Median ADC and swFF were significantly lower and median nDWI signal was significantly higher in biopsies with tumor cells versus nondetectable tumor cells (898 × 10−6 mm2/s vs 1617 × 10−6 mm2/s; 11.5% vs 62%; 5.3 vs 2.3, respectively; P < 0.001). Tumor cellularity inversely correlated with ADC and swFF, and positively correlated with nDWI signal (P < 0.001). In serial biopsies, taken before and after treatment, changes in multiparametric MRI parameters paralleled histological changes.

Conclusions

Multiparametric MRI provides valuable information about mCRPC bone metastases. These data further clinically qualify DWI as a response biomarker in mCRPC.
Multimodality Radionuclide Imaging in a Patient With Hereditary Paraganglioma-Pheochromocytoma Syndrome
Authors: Yim So Y. , Moncayo Valeria M. , Pasquel Francisco J. , Halkar Raghuveer K.
Published: September 2017

Hereditary paraganglioma (PGL)-pheochromocytoma (PCC) syndrome is a genetic disorder caused by a mutation of the tumor suppressor gene SDHD that results in a predisposition for head and neck PGLs and PCCs. We present a case of a 33-year-old woman where 18F-FDG PET/CT showed areas of increased uptake in both the adrenal and cervical regions, consistent with PCCs and PGLs, respectively. Further imaging revealed that PCCs were 123I-MIBG avid, whereas the PGLs were 111In-octreotide avid. This demonstrates the varying sensitivities of different imaging modalities in regard to neuroendocrine tumors and the potential for treatment using multiple targeted therapies.
Comparative Effectiveness of Ultrasonography, 99mTc-Sestamibi, and 18F-Fluorocholine PET/CT in Detecting Parathyroid Adenomas in Patients With Primary Hyperparathyroidism
Authors: Thanseer NTK , Bhadada Sanjay Kumar , Sood Ashwani , Mittal Bhagwant Rai , Behera Arunanshu , Gorla Arun Kumar Reddy , Kalathoorakathu Renjith R. , Singh Priyanka , Dahiya Divya , Saikia Uma Nahar , Rao Sudhaker D.
Published: September 2017

Purpose

Accurate preoperative localization of parathyroid lesion(s) is crucial for successful surgical management of primary hyperparathyroidism (PHPT). This study was conducted to compare the effectiveness of ultrasonography (USG) of the neck, 99mTc-sestamibi (MIBI) imaging with or without SPECT/CT, and 18F-fluorocholine (FCH) PET/CT imaging in the preoperative localization of parathyroid lesions in patients with PHPT.

Methods

Fifty-four consecutive patients with PHPT were included in this prospective study who underwent preoperative localization of the parathyroid lesion(s) using 3 diagnostic modalities followed by surgery. The sensitivity, positive predictive value, and accuracy of the 3 imaging procedures to accurately detect abnormal parathyroid glands were determined using histopathology as criterion standard with postoperative biochemical response confirmation.

Results

18F-fluorocholine PET/CT detected 52 of 54 patients and 52 of 56 lesions with histopathologically proven parathyroid adenomas on patient-based and lesion-based analysis, respectively. Preoperative USG, MIBI, and FCH PET/CT localized abnormal parathyroid gland(s) in 39 (72.2%), 43 (79.6%), and 54 (100%) patients, respectively. The sensitivity and positive predictive value were 69.3% and 87.1% for USG, 80.7% and 97.6% for MIBI, and 100% and 96.3% for FCH PET/CT. The accuracy was 62.9%, 79.6%, and 96.3% for USG, MIBI, and FCH PET/CT, respectively, in patient-wise analysis. In 6 patients with ectopic lesions, FCH PET/CT demonstrated higher sensitivity and accuracy than MIBI and USG (100% vs 66.6% and 16.7%, respectively).

Conclusions

Among the 3 imaging techniques tested simultaneously, FCH PET/CT was superior for accurate preoperative localization of parathyroid adenomas, especially for ectopic or small parathyroid lesions.
Tumour virology in the era of high-throughput genomics
Authors: Tang Ka-Wei , Larsson Erik
Published: September 2017

With the advent of massively parallel sequencing, oncogenic viruses in tumours can now be detected in an unbiased and comprehensive manner. Additionally, new viruses or strains can be discovered based on sequence similarity with known viruses. Using this approach, the causative agent for Merkel cell carcinoma was identified. Subsequent studies using data from large collections of tumours have confirmed models built during decades of hypothesis-driven and low-throughput research, and a more detailed and comprehensive description of virus–tumour associations have emerged. Notably, large cohorts and high sequencing depth, in combination with newly developed bioinformatical techniques, have made it possible to rule out several suggested virus–tumour associations with a high degree of confidence. In this review we discuss possibilities, limitations and insights gained from using massively parallel sequencing to characterize tumours with viral content, with emphasis on detection of viral sequences and genomic integration events.

This article is part of the themed issue ‘Human oncogenic viruses’.
Tumour viruses and innate immunity
Authors: Hopcraft Sharon E. , Damania Blossom
Published: September 2017

Host cells sense viral infection through pattern recognition receptors (PRRs), which detect pathogen-associated molecular patterns (PAMPs) and stimulate an innate immune response. PRRs are localized to several different cellular compartments and are stimulated by viral proteins and nucleic acids. PRR activation initiates signal transduction events that ultimately result in an inflammatory response. Human tumour viruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein–Barr virus, human papillomavirus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus type 1 and Merkel cell polyomavirus, are detected by several different PRRs. These viruses engage in a variety of mechanisms to evade the innate immune response, including downregulating PRRs, inhibiting PRR signalling, and disrupting the activation of transcription factors critical for mediating the inflammatory response, among others. This review will describe tumour virus PAMPs and the PRRs responsible for detecting viral infection, PRR signalling pathways, and the mechanisms by which tumour viruses evade the host innate immune system.

This article is part of the themed issue ‘Human oncogenic viruses’.
Human T-cell leukaemia virus type 1: parasitism and pathogenesis
Authors: Bangham Charles R. M. , Matsuoka Masao
Published: September 2017

Human T-cell leukaemia virus type 1 (HTLV-1) causes not only adult T-cell leukaemia-lymphoma (ATL), but also inflammatory diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 transmits primarily through cell-to-cell contact, and generates abundant infected cells in the host in order to survive and transmit to a new host. The resulting high proviral load is closely associated with the development of ATL and inflammatory diseases. To increase the number of infected cells, HTLV-1 changes the immunophenotype of infected cells, induces proliferation and inhibits apoptosis through the cooperative actions of two viral genes,
tax
and
HTLV-1 bZIP factor
(
HBZ
). As a result, infected cells survive, proliferate and infiltrate into the tissues, which is critical for transmission of the virus. Thus, the strategy of this virus is indivisibly linked with its pathogenesis, providing a clue for prevention and treatment of HTLV-1-induced diseases.

This article is part of the themed issue ‘Human oncogenic viruses’.
Viral hepatitis and liver cancer
Authors: Ringehan Marc , McKeating Jane A. , Protzer Ulrike
Published: September 2017

Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors.

This article is part of the themed issue ‘Human oncogenic viruses’.
Vibrio furnissii, an emerging pathogen causing acute gastroenteritis: a Case Report
Authors: Ballal Mamatha , Shetty Vignesh , Bangera Sohan Rodney , Prabhu Mukhyaprana , Umakanth Shashikiran
Published: September 2017

Introduction.
Vibrio furnissii is a motile, Gram-negative, oxidase-positive, halophilic bacteria first defined in 1977. It is ubiquitously present in marine environments and is one of the 11 non-cholera Vibrio species pathogenic in humans, which can lead to human gastroenteritis and extra-intestinal manifestations.

Case presentation. A 73-year-old female patient was admitted to the hospital with acute gastroenteritis after consumption of seafood, which later by microbiological investigations was confirmed as Vibrio furnissii, a member of the family Vibrionaceae. The patient was treated with oral doxycycline and ciprofloxacin.

Conclusion.
V. furnissii, an emerging pathogen known for quite some time as an aetiological agent responsible, for acute gastroenteritis cases yet to get more clinical attention. Descriptions of putative virulence factors of this pathogen are limited, and in-depth studies on the pathogenesis of V. furnissii need to be established.
Deletion of murine IQGAP1 results in increased mTOR activation and blunted ketogenic response
Authors: Erickson Hanna , Anakk Sayeepriyadarshini
Published: September 2017

IQ motif-containing GTPase Activating Protein 1 (IQGAP1) is a ubiquitously expressed scaffolding protein that integrates signaling from multiple cellular processes including motility, adhesion, and proliferation. Here, we show that IQGAP1 is induced in the liver upon fasting and can also regulate β-oxidation and ketone body synthesis. Utilizing ketogenic diet and pharmacologic activation we identified that hepatic PPARα activity is compromised inIqgap1-/-mice. Our data show that IQGAP1 interacts with the mechanistic target of rapamycin (mTOR) and IQGAP1 deletion results in enhanced mTOR complex 1 (mTORC1) activation. Conversely, ectopic expression of IQGAP1 inIqgap1-/-mice was sufficient to suppress mTORC1 signaling. We also confirmed that modulation of mTORC1 signaling by IQGAP1 is cell autonomous. This increased mTORC1 activation impedes PPARα signaling since mTORC1 inhibition restored a subset of metabolic genes inIqgap1-/-mice. Overall, we demonstrate a previously unidentified role for IQGAP1 as an important regulator of mTORC1 activity and long-term ketosis.
Comparison of seven single cell Whole Genome Amplification commercial kits using targeted sequencing
Authors: Biezuner Tamir , Raz Ofir , Amir Shiran , Milo Lilach , Adar Rivka , Fried Yael , Ainbinder Elena , Shapiro Ehud
Published: September 2017

Advances in biochemical technologies have led to a boost in the field of single cell genomics. Observation of the genome at a single cell resolution is currently achieved by pre-amplification using whole genome amplification (WGA) techniques that differ by their biochemical aspects and as a result by biased amplification of the original molecule. Several comparisons between commercially available single cell dedicated WGA kits (scWGA) were performed, however, these comparisons are costly, were only performed on selected scWGA kit and more notably, are limited by the number of analyzed cells, making them limited for reproducibility analysis. We benchmarked an economical assay to compare all commercially available scWGA kits that is based on targeted sequencing of thousands of genomic regions, including highly mutable genomic regions (microsatellites), from a large cohort of human single cells (125 cells in total). Using this approach, we could analyze the genome coverage, the reproducibility of genome coverage and the error rate of each kit. Our experimental design provides an affordable and reliable comparative assay that simulates a real single cell experiment. Results demonstrate the needfor a dedicated kit selection depending on the desired single cell assay.
Compensatory evolution facilitates the acquisition of multiple plasmids in bacteria
Authors: Santos-Lopez Alfonso , Bernabe-Balas Cristina , San Millan Alvaro , Ortega-Huedo Rafael , Hoefer Andreas , Ares-Arroyo Manuel , Gonzalez-Zorn Bruno
Published: September 2017

The coexistence of multicopy plasmids is a common phenomenon. However, the evolutionary forces promoting these genotypes are poorly understood. In this study, we have analyzed multiple ColE1 plasmids (pB1000, pB1005 and pB1006) coexisting withinHaemophilus influenzaeRdKW20 in all possible combinations. When transformed into the naïve host, each plasmid type presented a particular copy number and produced a specific resistance profile and biological cost, whether alone or coexisting with the other plasmids. Therefore, there was no fitness advantage associated with plasmid coexistence that could explain these common plasmid associations in nature. Using experimental evolution, we showed howH. influenzaeRd was able to completely compensate the fitness cost produced by any of these plasmids. Crucially, once the bacterium has compensated for a first plasmid, the acquisition of new multicopy plasmid(s) did not produced any extra biological cost. We argue therefore that compensatory adaptation pave the way for the acquisition of multiple coexisting ColE1 plasmids.

Importance

Antibiotic resistance is a major concern for human and animal health. Plasmids play a major role in the acquisition and dissemination of antimicrobial resistance genes. In this report we investigate, for the first time, how plasmids are capable to cohabit stably in populations. This coexistence of plasmids is driven by compensatory evolution alleviating the cost of a first plasmid, which potentiates the acquisition of further plasmids at no extra cost. This phenomenon explains the high prevalence of plasmids coexistance in wild type bacteria, which generates multiresistant clones and contributes to the maintenance and spread of antibiotic resistance genes within bacterial populations.
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

The 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

To 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

Parasitic 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

Cell 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.
Structure cristalline et analyses thermique et de surface Hirshfeld du diperchlorate de 4-azaniumyl-2,2,6,6-tétraméthylpipéridin-1-ium
Authors: Chebbi Hammouda , Boumakhla Abdessalem , Zid Mohamed Faouzi , Guesmi Abderrahmen
Published: September 2017

The synthesis of 4-azaniumyl-2,2,6,6-tetramethylpiperidin-1-ium diperchlorate, C9H22N22+·2ClO4−, was carried out from an aqueous reaction of perchloric acid with 4-amino-2,2,6,6-tetramethylpiperidine. This compound was characterized by TGA–DSC analysis and single-crystal X-ray diffraction. The piperidine ring of the dication adopts a chair conformation and the orientation of the C—NH3bond is equatorial. One of the two crystallographically independent perchlorate anions exhibits disorder [occupancies 0.625 (7) and 0.375 (7)]. The crystal packing is constituted by a succession of mixed layers parallel to the (-102) plane, made up of C9H22N22+dications and ClO4−anions. These ions are linked by normal and bifurcated N—H...O hydrogen bonds withR44(12) graph-set motifs, generating a two-dimensional network. The intermolecular interactions in the crystal structure were quantified and analysed using Hirshfeld surface analysis.
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

Clostridium 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.

Context

Rising drug prices are putting pressure on health care budgets. Policymakers are assessing how they can save money through generic drugs.

Methods

We 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.

Findings

The 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.

Conclusions

Governments 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

This 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

The 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

Historically, 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 Objective

Several 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.

Methods

We 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.

Results

A 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.

Conclusions

This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers.

Scientific Significance

rTMS 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)
A New Russian Holiday Has More Behind It Than National Unity: the Political Functions of Historical Commemorations
Authors: Omelicheva Mariya
Published: September 2017

This study seeks to address both the theoretical and empirical aspects of national holidays' selection. Noting a breadth of historical events that a state may choose to celebrate, this study asks how and why only some events are selected for national remembrance and commemoration. I answer this question by considering the role of national holidays in politics of history and memory and state‐ and nation‐building. Using an example of the Russian government replacing an established public holiday — the Revolution Day, celebrated on 7 November — with a new holiday — the National Unity Day, celebrated on 4 November — I set out to demonstrate how the choice of historical events for national celebration hinges on their potentiality to be reconstructed and deployed for the present political agendas.
The Manner of Their Going Prime Ministerial Exits from Lyne to Abbott
Authors: Wear Rae
Published: September 2017

The Manner of Their Going Prime Ministerial Exits from Lyne to Abbott. By Norman Abjorensen (North Melbourne: Australian Scholarly 2015) ISBN: 978‐1‐925333‐21‐3, pp.245.
Sex, Soldiers and the South Pacific, 1939–45: Queer Identities in Australia in the Second World War
Authors: Boucher Leigh
Published: September 2017

Sex, Soldiers and the South Pacific, 1939–45: Queer Identities in Australia in the Second World War. By Yorick Smaal (Basingstoke: Palgrave Macmillan, 2015), pp.xxi + 250. £60.00 (cloth).
The Second Rush: Mining and the Transformation of Australia
Authors: Eklund Erik
Published: September 2017

The Second Rush: Mining and the Transformation of Australia. By David Lee (Redland Bay, Qld: Connor Court, 2016), pp.463. ISBN 978‐1‐925501‐14‐8. AU$49.95 (cloth).
The Conscription Conflict and the Great War
Authors: Ginn Geoffrey A. C.
Published: September 2017

The Conscription Conflict and the Great War. Edited by Robin Archer, Joy Damousi, Murray Goot and Sean Scalmer (Melbourne: Monash University Publishing, 2016), pp.220. AU$34.95 (cloth).
Beyond Gallipoli. New Perspectives on Anzac
Authors: Fathi Romain
Published: September 2017

Beyond Gallipoli. New Perspectives on Anzac. Edited by Raelene Frances and Bruce Scates (Melbourne: Monash University Publishing, 2016), pp.xxii + 259, 17 illustrations. AU$34.95 (pb).
The Perfect Dictatorship: China in the 21st Century
Authors: Golley Jane
Published: September 2017

The Perfect Dictatorship: China in the 21st Century. By Stein Ringen (Hong Kong: Hong Kong University Press, 2016). £19.95 (pb).