bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation of Brachyspira spp. isolated from laying hens using PCR-based methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
Authors: Harms Monika , Schmidt Volker , Heydel Tilo , Hauptmann Jutta , Ahlers Christine , Bergmann Rene , Baums Christoph G.
Published: May 2018

Avian intestinal spirochetosis (AIS), an important but neglected disease in laying hens, is caused by Brachyspira pilosicoli, B. intermedia, and B. alvinipulli. Poultry are also frequently colonized by putatively nonpathogenic species such as B. murdochii and B. innocens. We evaluated the differentiation of Brachyspira species by 3 methods: sequencing of the reduced nicotinamide adenine dinucleotide (NADH) oxidase gene ( nox), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and a new multiplex (m)PCR targeting genes such as the tryptophanase A gene ( tnaA) and the p-aminobenzoyl-glutamate hydrolase subunit B gene ( abgB). Sequencing of 414 bp of the nox PCR amplification products generated from 41 pure cultures of avian Brachyspira isolates allowed presumptive species identification in 33 isolates with at least 99% identity in basic local alignment search tool analysis, including B. pilosicoli, B. intermedia, B. murdochii, B. innocens, and “ B. pulli”. MALDI-TOF MS analysis was found to be a reliable tool for differentiation after extension of the manufacturer’s database. In the mPCR, all isolates identified as B. pilosicoli and B. intermedia were positive for abgB and tnaA, respectively. The mPCR might be very useful in detecting Brachyspira species in mixed cultures including not only nonpathogenic species, such as B. innocens, but also one of the AIS pathogens. We found that MALDI-TOF MS analysis combined with the mPCR targeting tnaA and abgB was suitable for the identification of avian isolates of B. pilosicoli and B. intermedia, 2 important agents of AIS.
Human Factors in the Privacy and Security of the Internet of Things
Authors: Chong Isis , Xiong Aiping , Proctor Robert W.
Published: May 2018

The “Internet of things” (IoT) refers to Internet-enabled technologies designed to increase the efficiency of users’ lives by communicating with other objects and elements in a system. The growth in these interconnected devices has been matched with increases in the use and aggregation of data collected by vendors or third parties. The number of hackers attempting to access users’ private information also has grown. Although attempts have been made to increase IoT security, the role users can play in protecting their information has been overlooked. We illustrate the necessity of taking a user-centered approach to privacy and security when designing and developing IoT technologies.
Generalizability and Decision Studies of a Treatment Adherence Instrument
Authors: Southam-Gerow Michael A. , Bonifay Wes , McLeod Bryce D. , Cox Julia R. , Violante Stephanie , Kendall Philip C. , Weisz John R.
Published: May 2018

Observational measurement of treatment adherence has long been considered the gold standard. However, little is known about either the generalizability of the scores from extant observational instruments or the sampling needed. We conducted generalizability (G) and decision (D) studies on two samples of recordings from two randomized controlled trials testing cognitive–behavioral therapy for youth anxiety in two different contexts: research versus community. Two doctoral students independently coded 543 session recordings from 52 patients treated by 13 therapists. The initial G-study demonstrated that context accounted for a disproportionately large share of variance, so we conducted G- and D-studies for the two contexts separately. Results suggested that reliable cognitive–behavioral therapy adherence studies require at least 10 sessions per patient, assuming 12 patients per therapists and two coders—a challenging threshold even in well-funded research. Implications, including the importance of evaluating alternatives to observational measurement, are discussed.
Treating ADHD With Suggestion: Neurofeedback and Placebo Therapeutics
Authors: Thibault Robert T. , Veissière Samuel , Olson Jay A. , Raz Amir
Published: May 2018

Objective: We propose that clinicians can use suggestion to help treat conditions such as ADHD. Methods: We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. Results: The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Conclusion: Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential alternative to current standard of care for individuals with ADHD.
The European Parliament and the eurozone crisis: An exceptional actor?
Authors: Warren Thomas
Published: May 2018

The eurozone crisis has reinvigorated the debate over the requirement for supranational integration within the single currency area. With the focus of political scientists often restricted to the study of intergovernmental processes of crisis management, this article considers the role of the European Parliament during the key legislative negotiations on European Union fiscal governance reform. A comparative frame analysis of the major European Union institutions’ crisis discourse is applied. Frames are linked to macroeconomic ideology as well as to different integration scenarios within Economic and Monetary Union. It is found that the European Parliament converged around limited framing devices supporting intergovernmental fiscal discipline. Key explanatory factors here were the ideological divisions among Members of the European Parliament as well as the leadership role played by the European Council. These findings are broadly consistent with the new intergovernmentalist claims that the supranational institutions are no longer hard-wired to the pursuit of supranational integration.
China Registry of Hepatitis B (CR-HepB): Protocol and implementation of a nationwide hospital-based registry of hepatitis B
Authors: Shan Shan , Wei Wei , Kong Yuanyuan , Niu Junqi , Shang Jia , Xie Wen , Zhang Yuexin , Ren Hong , Tang Hong , Ding Huiguo , Nan Yuemin , Dou Xiaoguang , Han Tao , Xu Xiaoyuan , Duan Zhongping , Wei Lai , Hou Jinlin , Zhuang Hui , You Hong , Jia Jidong ,   for the CR-Hepb Study Group, Beijing, China
Published: May 2018

Aims: The disease burden of chronic HBV infection in China remains high, although the rate of new infections has become extremely low. To facilitate real-world clinical study of chronic HBV infection, we established a nationwide hospital-based electronic platform, named the China Registry of Hepatitis B (CR-HepB). Methods: This internet-based registry for chronic hepatitis B recruited patients from tertiary or secondary hospitals that have particular interest and expertise in managing hepatitis B patients. The main inclusion criteria for the database were men or women with hepatitis B surface antigen positivity ≥ 6 months, hepatitis B e antigen positive or negative, with or without cirrhosis, and with or without treatment. At the first time of data entry, demographics, medical history, virology, biochemistry, hematology and radiology reports, as well as diagnosis and treatment information, are recorded. Registered patients then receive a standard of care and follow-up every three (optional) to six months (required) for changes in virology, biochemistry and radiology, as well as clinical progression. Results and Conclusions: To date, 47 hospitals have joined the CR-HepB. This platform can be used to demonstrate the clinical pattern and treatment profile of chronic HBV infection, evaluate long-term efficacy and safety of antiviral therapy and provide real-world evidence for policy-making in China. Trial registration: ClinicalTrials.gov ID: NCT03108794
Entrepreneurial storying
Authors: Markowska Magdalena , Lopez-Vega Henry
Published: May 2018

Context and entrepreneurship are intertwined. In some contexts, the ability to craft a compelling regional identity story may become crucial for enacting entrepreneurial action. Building on an in-depth case study of the recent revival of a Spanish wine region, we analyze the interaction between regional context (i.e. regional identity) and entrepreneurial behavior. We find that to facilitate the creation of conducive conditions for entrepreneurial action, entrepreneurs craft regional identity stories. We show that stories both reflect and possess agency and propose that storying is a process of constructing new identity stories. Specifically, we identify three different types of narratives and observe that the local winepreneurs actively engage in storying—that is, contextualizing the story to their needs.
Association of angiotensin-converting enzyme gene I/D polymorphism with chronic obstructive pulmonary disease: a meta-analysis
Authors: Xu Guodong , Fan Guohui , Sun Yingtong , Yu Lili , Wu Sinan , Niu Wenquan
Published: May 2018

Objectives:

We conducted a meta-analysis of published studies on the angiotensin-converting enzyme ( ACE) gene insertion/deletion (I/D) polymorphism associated with the risk of chronic obstructive pulmonary disease, as well as with pulmonary function and circulating angiotensin-converting enzyme changes.

Methods:

A literature search, quality assessment and data extraction were completed independently and in duplicate.

Results:

A total of 16 articles were meta-analysed, including 12 articles (2113 patients and 8786 controls) for chronic obstructive pulmonary disease risk and eight articles (11,664 subjects) for pulmonary and circulating phenotypes. In overall and subgroup analyses, no significance was noted between the I/D polymorphism and chronic obstructive pulmonary disease risk under all genetic models ( P>0.05), without heterogeneity or publication bias. Carriers of II, ID and II plus ID genotypes had significantly lower levels of circulating angiotensin-converting enzyme than those with the DD genotype (weighted mean difference −13.35, −8.13 and −10.74 U/L, respectively, P<0.001). For forced expiratory volume in one second (FEV1)/forced vital capacity, carriers of the DD genotype had marginally lower levels than those with the DD genotype (weighted mean difference –1.66, P=0.034). Furthermore in the case of FEV1 of 50% or greater of predicted FEV1, FEV1 was marginally lower in ID genotype carriers than DD genotype carriers (weighted mean difference −3.50, P=0.056).

Conclusions:

Our meta-analytical findings demonstrated that the ACE gene I/D polymorphism was not associated with the risk of chronic obstructive pulmonary disease.
High Reintervention and Amputation Rates After Outpatient Atherectomy for Claudication
Authors: Mukherjee Dipankar , Contos Brian , Emery Erica , Collins Devon T. , Black James H.
Published: May 2018

Outpatient use of atherectomy for peripheral arterial disease has grown rapidly and outcomes are poorly understood. We analyzed outcomes of atherectomy done for claudication, comparing office and hospital outpatient settings. Analysis of Medicare Part B claims data was performed for incident femoral–popliteal or tibial–peroneal atherectomy from 2012 to 2014. Longitudinal analysis assessed services 18 months before, during, and up to 18 months after the incident peripheral vascular intervention (PVI). Differences between office-based and hospital outpatient-based settings were assessed using χ2 and Fisher exact tests. Comparing procedure settings, significant differences in race (femoral–popliteal: P = .04, tibial–peroneal: P = .001), chronic renal failure (femoral–popliteal: P = .002), and hypertension (femoral–popliteal: P = .01, tibial–peroneal: P = .006) were found. Nine hundred twenty-four patients undergoing femoral–popliteal atherectomy were analyzed (262 office based, 662 hospital outpatient based); 42.7% of office-based and 36.9% of hospital outpatient-based femoral–popliteal atherectomy patients had repeat PVI within 18 months ( P = .10). Major amputation was performed in 2.3% and 3.2% of patients in office and hospital outpatient settings, respectively ( P = .47). Four hundred twenty-three patients undergoing tibial–peroneal atherectomy were analyzed (202 office based, 221 hospital outpatient based); 46.5% of office-based and 38.9% of hospital outpatient-based tibial–peroneal atherectomy patients had repeat PVI within 1 year ( P = .11). Major amputation was performed in 5.0% and 8.1% of patients in office and hospital outpatient settings, respectively ( P = .19). Our study demonstrates higher than expected rates of major amputation for patients undergoing peripheral arterial atherectomy with regard to previously reported rates. Further studies may be required to prove the efficacy and safety of atherectomy for occlusive disease in the femoral–popliteal and tibial–peroneal segments to ensure outcomes are not worse than the natural history of medically managed claudicants.
Who Decides What Is Acceptable Speech on Campus? Why Restricting Free Speech Is Not the Answer
Authors: Ceci Stephen J. , Williams Wendy M.
Published: May 2018

Recent protests on dozens of campuses have led to the cancellation of controversial talks, and violence has accompanied several of these protests. Psychological science provides an important lens through which to view, understand, and potentially reduce these conflicts. In this article, we frame opposing sides’ arguments within a long-standing corpus of psychological research on selective perception, confirmation bias, myside bias, illusion of understanding, blind-spot bias, groupthink/in-group bias, motivated skepticism, and naive realism. These concepts inform dueling claims: (a) the protestors’ violence was justified by a higher moral responsibility to prevent marginalized groups from being victimized by hate speech, versus (b) the students’ right to hear speakers was infringed upon. Psychological science cannot, however, be the sole arbiter of these campus debates; legal and philosophical considerations are also relevant. Thus, we augment psychological science with insights from these literatures to shed light on complexities associated with positions supporting free speech and those protesting hate speech. We conclude with a set of principles, most supported by empirical research, to inform university policies and help ensure vigorous freedom of expression within the context of an inclusive, diverse community.
Animacy and attentional processes: Evidence from the Stroop task
Authors: Bugaiska Aurélia , Grégoire Laurent , Camblats Anna-Malika , Gelin Margaux , Méot Alain , Bonin Patrick
Published: May 2018

In visual perception, evidence has shown that attention is captured earlier and held longer by animate than inanimate stimuli. The former are also remembered better than the latter. Thus, as far as attentional processes are concerned, animate entities have a privileged status over inanimate entities. We tested this hypothesis further using an adaptation of the Stroop paradigm. Adults had to categorise the colours of words that referred to either animate or inanimate concepts. In two experiments, we found that it took longer to process the ink colour of animate than inanimate words. Indeed, this effect was found when the words were presented in an oral animacy Stroop task (Experiment 1) and in a manual animacy Stroop task (Experiment 2). Using ex-Gaussian analyses and examining the distribution of RTs as a function of vincentiles per animacy condition, we did not find a specific localisation of the animacy effect. The findings are interpreted as providing further evidence that animates are prioritised in processing because their fitness value is higher than that of inanimates.
Female combatants, forced recruitment, and civil conflict outcomes
Authors: Braithwaite Alex , Ruiz Luna B.
Published: May 2018

Women participated as combatants in almost 40% of civil conflicts that occurred between 1979 and 2009. We offer a novel argument about the effect of female combatants upon the outcomes of the civil conflicts that they join. Groups that recruit female combatants are more likely to achieve victory in their conflicts than are groups that do not recruit female combatants. However, when rebel groups rely upon forced recruitment, they risk undermining the benefits associated with female combatants, lowering their likelihood of victory relative to that of the government. We test this conditional argument using multinomial logistic regression models on a sample of 194 rebel groups globally from 1979 to 2009. We find that female participation appears to decrease the likelihood of government victory in civil wars; this effect holds primarily in instances in which female participation could plausibly be thought of as voluntary. Forced female participation, by contrast, appears to increase the likelihood of a government victory.
Predicting Civic Competencies Among East African Youth and Emerging Adults: Report on the Swahili General Self-Efficacy Scale
Authors: Johnson Laura R. , Johnson-Pynn Julie S. , Drescher Christopher F. , Sackey Enoch , Assenga Sophia
Published: May 2018

Self-efficacy has been examined around the world, with research indicating its importance for personal and civic development. The General Self-Efficacy Scale has been translated into 33 languages; however, no African language version has been well established, and research on self-efficacy in the region is rare. A measure of self-efficacy in Swahili, a language widely used in East Africa, could spur research. We describe the development of the Swahili General Self-Efficacy Scale and its psychometric properties with a large, diverse group of Tanzanian youth and emerging adults ( N = 1,409, ages 13–26). We report psychometrics including internal consistency, factor structure, convergent reliability, and the ability of the measure to predict civic competencies. Our results establish the Swahili General Self-Efficacy Scale as a credible measure with implications for personal and civic development. We suggest areas for investigation and provide the Swahili scale as an impetus for research in the region.
Takotsubo Cardiomyopathy Mimicking Stent Thrombosis After Percutaneous Coronary Intervention
Authors: Khattak Furqan , Khalid Muhammad , Murtaza Ghulam , Paul Timir K.
Published: May 2018

Takotsubo cardiomyopathy, also known as “broken heart syndrome,” is a transient left ventricular dysfunction associated with stress (usually emotional) induced myocardial injury and stunning. It often presents as myocardial infarction on surface electrocardiogram (EKG). Diagnosis is made by coronary angiography, which rules out coronary artery disease and shows pathognomonic apical ballooning. In this article, we present a case of a 72-year-old woman who initially presented with an ST segment elevation myocardial infarction on EKG. Coronary angiography showed severe left anterior descending artery and diagonal lesions requiring percutaneous coronary intervention. Post–percutaneous coronary intervention, EKG changes resolved. The next day, the patient developed recurrent chest pain and her EKG showed diffuse T-wave inversion in precordial leads with reemerging ST segment elevations concerning for stent thrombosis. The patient underwent repeat emergent coronary angiography, which showed patent stents and findings consistent with takotsubo cardiomyopathy.
A Critical Review on the Concept of Avapeedaka Snehapana, a Special Mode of Lipid Administration
Authors: Kadambari P. B. , Dharmarajan Prasanth , Prathibha C. K. , Anandaraman P. V.
Published: May 2018

Avapeedaka Snehapana is a unique and special method of internal administration of Sneha dravya (unctuous medicine) mentioned in the classical ayurveda texts. It is mainly indicated in mutravegarodha janya vikara (diseases due to the suppression of urge of micturition). Because of the lack of adequate review and analysis, this method of administration of snehapana (internal administration of lipid) is losing its significance from the practices and the concept remains unexplored. The reasons for not being practiced like other snehana (oleation therapy) procedures are because of the less understanding of the concept of administration, scattered and minimal textual references. Through this review, we intend to have a detailed analysis on the concept of avapeedaka snehapana mentioned in the Brihatrayees (Caraka Samhita, Sushruta Samhita, and Ashtanga Hridaya—the 3 main texts of ayurveda) with its possible practical methods of administration. The role of ghrita (ghee) in inducing the ketogenesis is also analyzed. Being a ketogenic diet, the benefits of ghrita are interpreted. These efforts may help bring down avapeedaka snehapana into the mainstream of practice.
International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia
Authors: Hrusak Ondrej , de Haas Valerie , Stancikova Jitka , Vakrmanova Barbora , Janotova Iveta , Mejstrikova Ester , Capek Vaclav , Trka Jan , Zaliova Marketa , Luks Ales , Bleckmann Kirsten , Möricke Anja , Irving Julie , Konatkowska Benigna , Alexander Thomas B. , Inaba Hiroto , Schmiegelow Kjeld , Stokley Simone , Zemanova Zuzana , Moorman Anthony V. , Rossi Jorge Gabriel , Felice Maria Sara , Dalla-Pozza Luciano , Morales Jessa , Dworzak Michael , Buldini Barbara , Basso Giuseppe , Campbell Myriam , Cabrera Maria Elena , Marinov Neda , Elitzur Sarah , Izraeli Shai , Luria Drorit , Feuerstein Tamar , Kolenova Alexandra , Svec Peter , Kreminska Olena , Rabin Karen R. , Polychronopoulou Sophia , da Costa Elaine , Marquart Hanne Vibeke , Kattamis Antonis , Ratei Richard , Reinhardt Dirk , Choi John K. , Schrappe Martin , Stary Jan
Published: May 2018

Key Points

The largest cohort of ambiguous leukemias to date reveals a better prognosis of children who started on lymphoid-directed treatment. Myeloid-type primary treatment correlated with dismal outcomes in CD19+ leukemias.
Metabolic heterogeneity on baseline 18FDG-PET/CT scan is a predictor of outcome in primary mediastinal B-cell lymphoma
Authors: Ceriani Luca , Milan Lisa , Martelli Maurizio , Ferreri Andrés J. M. , Cascione Luciano , Zinzani Pier Luigi , Di Rocco Alice , Conconi Annarita , Stathis Anastasios , Cavalli Franco , Bellei Monica , Cozens Kelly , Porro Elena , Giovanella Luca , Johnson Peter W. , Zucca Emanuele
Published: May 2018

Key Points

MH on 18FDG-PET/CT may be a prognostic tool for PMBCL. High TLG combined with high MH at presentation identifies patients at high risk for progression after conventional therapy.
The social biography of antibiotic use in smallholder dairy farms in India
Authors: Chauhan Abhimanyu Singh , George Mathew Sunil , Chatterjee Pranab , Lindahl Johanna , Grace Delia , Kakkar Manish
Published: May 2018

Background

Antimicrobial resistance (AMR) has been identified as one of the major threats to global health, food security and development today. While there has been considerable attention about the use and misuse of antibiotics amongst human populations in both research and policy environments, there is no definitive estimate of the extent of misuse of antibiotics in the veterinary sector and its contribution to AMR in humans. In this study, we explored the drivers ofirrational usage of verterinary antibiotics in the dairy farming sector in peri-urban India.

Methods and materials

The study was conducted in the peri-urban belts of Ludhiana, Guwahati and Bangalore. A total of 54 interviews (formal and non-formal) were carried out across these three sites. Theme guides were developed to explore different drivers of veterinary antimicrobial use. Data was audio recorded and transcribed. Analysis of the coded data set was carried out using AtlasTi. Version 7. Themes emerged inductively from the set of codes.

Results

Findings were presented based on concept of ‘levels of analyses’. Emergent themes were categorised as individual, health systems, and policy level drivers. Low level of knowledge related to antibiotics among farmers, active informal service providers, direct marketing of drugs to the farmers and easily available antibiotics, dispensed without appropriate prescriptions contributed to easy access to antibiotics, and were identified to be the possible drivers contributing to the non-prescribed and self-administered use of antibiotics in the dairy farms.

Conclusions

Smallholding dairy farmers operated within very small margins of profits. The paucity of formal veterinary services at the community level, coupled with easy availability of antibiotics and the need to ensure profits and minimise losses, promoted non-prescribed antibiotic consumption. It is essential that these local drivers of irrational antibiotic use are understood in order to develop interventions and policies that seek to reduce antibiotic misuse.
Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient–Level Data
Authors: Lambertini Matteo , Moore Halle C.F. , Leonard Robert C.F. , Loibl Sibylle , Munster Pamela , Bruzzone Marco , Boni Luca , Unger Joseph M. , Anderson Richard A. , Mehta Keyur , Minton Susan , Poggio Francesca , Albain Kathy S. , Adamson Douglas J.A. , Gerber Bernd , Cripps Amy , Bertelli Gianfilippo , Seiler Sabine , Ceppi Marcello , Partridge Ann H. , Del Mastro Lucia
Published: May 2018

Purpose

The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient–level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer.

Methods

The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model.

Results

A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups.

Conclusion

Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
Genetic Characterization of GnRH/LH-Responsive Primary Aldosteronism
Authors: Gagnon Nadia , Cáceres-Gorriti Katia Y , Corbeil Gilles , El Ghoyareb Nada , Ludwig Natasha , Latour Mathieu , Lacroix André , Bourdeau Isabelle
Published: May 2018

Background

Recently, somatic β-catenin mutations (CTNNB1) identified in aldosterone-producing adenomas (APAs) from three women were suggested to be responsible for the aberrant overexpression of luteinizing hormone/choriogonadotropin receptor and gonadotropin-releasing hormone receptor in the APA.

Objective

To genetically characterize patients with primary aldosteronism (PA) evaluated in vivo for gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH)-responsive aldosterone secretion.

Method

Patients with PA were evaluated in vivo to determine the possible regulation of aldosterone secretion by GnRH or LH. Genetic analysis of the CTNNB1, KCNJ5, ATP1A1, ATP2B3, CACNA1D, and GNAS genes were performed in this cohort and a control cohort of PA not tested in vivo for GnRH response.

Results

We studied 50 patients with confirmed PA, including 36 APAs, 12 bilateral macronodular adrenal hyperplasias, 1 oncocytoma, and 1 bilateral hyperplasia with cosecretion of cortisol. Among 23 patients tested in vivo for GnRH response of aldosterone, 7 (30.4%) had a positive response, 4 (17.4%) a partial response, and 12 (52.2%) no response. No somatic CTNNB1 mutations were identified, but the disease-causing c.451G>C KCNJ5 mutation was found in two individuals with partial and no GnRH responses and an individual showing a positive response to LH. Two additional somatic pathogenic mutations, CACNA1D c.776T>A and ATP1A1 c.311T>G, were identified in two patients with no GnRH responses. In the 26 patients not tested for GnRH response, we identified 2 CTNNB1 (7.7%), 13 KCNJ5 (50%), and 1 CACNA1D (3.8%) mutations.

Conclusion

Aberrant regulation of aldosterone by GnRH is frequent in PA, but is not often associated with somatic CTNNB1, although it may be found with somatic KCNJ5 mutations.
Hypertriglyceridemia in Diabetes Mellitus: Implications for Pediatric Care
Authors: Hartz Jacob C , de Ferranti Sarah , Gidding Samuel
Published: May 2018

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). It is estimated that the risk of CVD in diabetes mellitus (DM) is 2 to 10 times higher than in the general population. Much of this increased risk is thought to be related to the development of an atherogenic lipid profile, in which hypertriglyceridemia is an essential component. Recent studies suggest that dyslipidemia may be present in children and adolescents with DM, particularly in T2DM and in association with poor control in T1DM. However, the role of hypertriglyceridemia in the development of future CVD in youth with DM is unclear, as data are scarce. In this review, we will evaluate the pathophysiology of atherogenic hypertriglyceridemia in DM, the evidence regarding an independent role of triglycerides in the development of CVD, and the treatment of hypertriglyceridemia in patients with DM, highlighting the potential relevance to children and the need for more data in children and adolescents to guide clinical practice.
A Mechanism for Eliciting Second-Order Beliefs and the Inclination to Choose
Authors: Karni Edi
Published: May 2018

This paper describes a direct revelation mechanism for eliciting decision makers' introspective beliefs on sets of subjective prior or posterior probabilities. The proposed scheme constitutes a revealed-preference procedure for measuring the inclination of decision makers to choose one alternative over another modeled by Minardi and Savochkin (2015). (JEL D11, D82, D83)
A dosimetric evaluation on applying RTOG-based and CT/MRI-based delineation methods to brachial plexus in radiotherapy of nasopharyngeal carcinoma treated with helical tomotherapy
Authors: Li Chi-Him , Wu Vincent WC , Chiu George
Published: May 2018

Objective:

In radiotherapy of nasopharyngeal carcinoma (NPC) patients, the brachial plexus (BP) situated at both sides of the neck is often irradiated to high dose. This study was to evaluate different BP delineation methods and analyse the dosimetric consequences when applying BP dose constraints in radiotherapy planning of NPC.

Methods:

15 NPC cases radically treated with helical tomotherapy were recruited. Apart from the original treatment plan (Plan A), two new plans (Plans B and C) with additional BP dose constraints were computed using the same planning CT images, structures and planning parameters. Plan B consisted of BP contours based on Radiation Therapy Oncology Group (RTOG)-endorsed atlas; while those in Plan C were based on MR images registered with the planning CT images.

Results:

The mean BP volume by RTOG method was 19.04 ± 3.50 cm3  vs 10.44 ± 2.00 cm3 by CT/MRI method. The mean BP overlapping volume between the two contouring methods was 1.9 cm3 (0.38–4.03 cm3). There was significant difference between two methods (p < 0.001). The average D  max, D  mean, D  5%, D  10% and D  15% of both sides of BP in Plan A were significantly higher than those in both Plan B and Plan C. There were no significant dose differences in the targets and organs at risk (OARs) after applying dose constraints in Plan B and Plan C.

Conclusion:

RTOG method was recommended since larger BP volume provided better protection. Applying BP dose constraints during tomotherapy plan optimisation for NPC patients could significantly reduce the BP dose (p < 0.05) without compromising the doses to the targets and other OARs.

Advances in knowledge:

This is the first study comparing the delineation method based on RTOG-endorsed atlas with the conventional CT/MRI delineation method for BP in tomotherapy of NPC patients. Our results showed that BP dose could be significantly reduced after applying the dose constraints without compromising the doses to the target volumes and other OARs. The RTOG method was more favoured as it gave a relatively larger BP volume and therefore offered better organ sparing.
MicroRNA-focused CRISPR-Cas9 library screen reveals fitness-associated miRNAs
Authors: Kurata Jessica S. , Lin Ren-Jang
Published: May 2018

MicroRNAs (miRNAs) are post-transcriptional gene regulators that play important roles in the control of cell fitness, differentiation, and development. The CRISPR-Cas9 gene-editing system is composed of the Cas9 nuclease in complex with a single guide RNA (sgRNA) and directs DNA cleavage at a predetermined site. Several CRISPR-Cas9 libraries have been constructed for genome-scale knockout screens of protein function; however, few libraries have included miRNA genes. Here we constructed a miRNA-focused CRISPR-Cas9 library that targets 1594 (85%) annotated human miRNA stem–loops. The sgRNAs in our LX-miR library are designed to have high on-target and low off-target activity, and each miRNA is targeted by four to five sgRNAs. We used this sgRNA library to screen for miRNAs that affect cell fitness of HeLa or NCI-N87 cells by monitoring the change in frequency of each sgRNA over time. By considering the expression in the tested cells and the dysregulation of the miRNAs in cancer specimens, we identified five HeLa pro-fitness and cervical cancer up-regulated miRNAs (miR-31-5p, miR-92b-3p, miR-146b-5p, miR-151a-3p, and miR-194-5p). Similarly, we identified six NCI-N87 pro-fitness and gastric cancer up-regulated miRNAs (miR-95-3p, miR-181a-5p, miR-188-5p, miR-196b-5p, miR-584-5p, and miR-1304-3p), as well as three anti-fitness and down-regulated miRNAs (let-7a-3p, miR-100-5p, and miR-149-5p). Some of those miRNAs are known to be oncogenic or tumor-suppressive, but others are novel. Taken together, the LX-miR library is useful for genome-wide unbiased screening to identify miRNAs important for cellular fitness and likely to be useful for other functional screens.
Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson’s disease
Authors: Dourmashkin Robert R. , McCall Sherman A. , Dourmashkin Neil , Hannah Matthew J.
Published: May 2018

Background: In a previous study on encephalitis lethargica, we identified a virus related to enterovirus in autopsy brain material. Transmission electron microscopy (TEM), immunohistochemistry (IHC) and molecular analysis were employed.  Our present objective was to investigate, using a similar approach, as to whether virus-like particles (VLP) and enterovirus antigen are present in Parkinson’s disease (PD) brainstem neurons.

Methods: Fixed tissue from autopsy specimens of late onset PD and control brainstem tissue were received for study. The brain tissue was processed for TEM and IHC according to previous published methods.

Results:  We observed VLP in the brainstem neurons of all the cases of PD that were examined.  In the neurons’ cytoplasm there were many virus factories consisting of VLP and endoplasmic reticulum membranes. In some neurons, the virus factories contained incomplete VLP. Complete VLP in some neurons’ virus factories had an average diameter of 31 nm, larger than control brain ribosomes. In the nuclei, there were VLP with an average diameter of 40 nm. In cases of human poliomyelitis, there were cytoplasmic virus factories and intranuclear virus particles similar to those observed in PD. On preparing PD brain sections for IHC there was positive staining using anti-poliovirus antibody and anti-coxsackie antibody. This result was statistically significant.

Conclusions: We present evidence for an enterovirus infection in PD.  For future studies, virus isolation and molecular analysis are suggested.
Proteome-wide analysis of protein abundance and turnover remodelling during oncogenic transformation of human breast epithelial cells
Authors: Ly Tony , Endo Aki , Brenes Alejandro , Gierlinski Marek , Afzal Vackar , Pawellek Andrea , Lamond Angus I.
Published: May 2018

Background: Viral oncogenes and mutated proto-oncogenes are potent drivers of cancer malignancy. Downstream of the oncogenic trigger are alterations in protein properties that give rise to cellular transformation and the acquisition of malignant cellular phenotypes. Developments in mass spectrometry enable large-scale, multidimensional characterisation of proteomes. Such techniques could provide an unprecedented, unbiased view of how oncogene activation remodels a human cell proteome.

Methods: Using quantitative MS-based proteomics and cellular assays, we analysed how transformation induced by activating v-Src kinase remodels the proteome and cellular phenotypes of breast epithelial (MCF10A) cells. SILAC MS was used to comprehensively characterise the MCF10A proteome and to measure v-Src-induced changes in protein abundance across seven time-points (1-72 hrs). We used pulse-SILAC MS (Boisvert et al., 2012), to compare protein synthesis and turnover in control and transformed cells. Follow-on experiments employed a combination of cellular and functional assays to characterise the roles of selected Src-responsive proteins.

Results: Src-induced transformation changed the expression and/or turnover levels of ~3% of proteins, affecting ~1.5% of the total protein molecules in the cell. Transformation increased the average rate of proteome turnover and disrupted protein homeostasis. We identify distinct classes of protein kinetics in response to Src activation. We demonstrate that members of the polycomb repressive complex 1 (PRC1) are important regulators of invasion and migration in MCF10A cells. Many Src-regulated proteins are present in low abundance and some are regulated post-transcriptionally. The signature of Src-responsive proteins is highly predictive of poor patient survival across multiple cancer types. Open access to search and interactively explore all these proteomic data is provided via the EPD database (www.peptracker.com/epd).

Conclusions: We present the first comprehensive analysis measuring how protein expression and protein turnover is affected by cell transformation, providing a detailed picture at the protein level of the consequences of activation of an oncogene.
Comparing the temporal relationship of structural and functional connectivity changes in different adult human brain networks: a single-case study
Authors: Watanabe Takamitsu , Rees Geraint
Published: May 2018

Background: Despite accumulated evidence for adult brain plasticity, the temporal relationships between large-scale functional and structural connectivity changes in human brain networks remain unclear.

Methods: By analysing a unique richly detailed 19-week longitudinal neuroimaging dataset, we tested whether macroscopic functional connectivity changes lead to the corresponding structural alterations in the adult human brain, and examined whether such time lags between functional and structural connectivity changes are affected by functional differences between different large-scale brain networks.

Results: In this single-case study, we report that, compared to attention-related networks, functional connectivity changes in default-mode, fronto-parietal, and sensory-related networks occurred in advance of modulations of the corresponding structural connectivity with significantly longer time lags. In particular, the longest time lags were observed in sensory-related networks. In contrast, such significant temporal differences in connectivity change were not seen in comparisons between anatomically categorised different brain areas, such as frontal and occipital lobes. These observations survived even after multiple validation analyses using different connectivity definitions or using parts of the datasets.

Conclusions: Although the current findings should be examined in independent datasets with different demographic background and by experimental manipulation, this single-case study indicates the possibility that plasticity of macroscopic brain networks could be affected by cognitive and perceptual functions implemented in the networks, and implies a hierarchy in the plasticity of functionally different brain systems.
The reasons for use of cannabinoids and stimulants in patients with schizophrenia
Authors: Simonienko Katarzyna , Wygnał Natalia , Cwalina Urszula , Kwiatkowski Mikołaj , Szulc Agata , Waszkiewicz Napoleon
Published: May 2018

Cel pracy

Zarówno zażywanie kannabinoidów, jak i substancji psychoaktywnych z grupy stymulantów może mieć istotny wpływ na indukcję, przebieg oraz leczenie samej choroby, ale i być traktowane jako samoleczenie. Wielu pacjentów odczuwa subiektywne korzyści płynące ze stosowania tych środków w obszarach kompetencji społecznych, radzenia sobie ze skutkami ubocznymi neuroleptyków, stresem wpisanym w przebiegu choroby psychicznej czy kontroli niektórych jej objawów. Niniejsza praca poświęcona jest przyczynom zażywania wspomnianych substancji psychoaktywnych przez pacjentów chorych na schizofrenię.

Metoda

przebadano 50 pacjentów chorych na schizofrenię, z których wszyscy zażywali substancje z grupy kannabinoidów, a 25- także z grupy stymulantów. Wypełnili oni kwestionariusze dotyczące przyczyn zażywania narkotyków oraz subiektywnie odczuwanych dolegliwości psychicznych. Przeanalizowano dokumentację medyczną.

Wyniki

Stwierdzono, że grupa zażywająca SPA z grup kannabinoidów i stymulantów, wskazywała duchowość jako przyczynę istotnie częściej w stosunku do grupy zażywającej wyłącznie kannabinoidy. Palący marihuanę i haszysz istotnie częściej jako cel deklarowali poprawę relacji społecznych. W obu grupach najczęstszą przyczyną była ciekawość, potrzeba zrelaksowania się, a także rozwiązywanie problemów , poprawa relacji międzyludzkich czy środek „na nieśmiałość”. W grupie używającej same kannabinoidy stwierdzono, że ludzie, którzy czuli się nierozumiani przez innych, często palili marihuanę, aby ułatwić sobie rozwiązywanie problemów. Osoby zażywające stymulanty skarżyły się często na słabą koncentrację uwagi.

Wnioski

Nieświadomość konsekwencji, jakie może wywołać zarówno używanie środków psychoaktywnych u osób obciążonych ryzykiem choroby psychicznej lub na nią chorującym jest dodatkowym czynnikiem ryzyka. Wyniki mogą wskazywać na zwiększone zapotrzebowanie na psychoedukację i wsparcie społeczne dotyczące wielu dziedzin życia pacjentów cierpiących na schizofrenię.
The Jagiellonian Idea and the Project for the Future
Authors: Kieniewicz Jan
Published: May 2018

The Jagiellonian Idea and the Project for the Future
The Polish community suffers from weakening national bonds and therefore it has difficulties with defining its identity. Grandiose declarations are an embarrassing confirmation of this fact. No great idea capable of raising a future project for Poland is apparent. Is the Jagiellonian Idea capable of strengthening bonds, perhaps of giving impulse to a metamorphosis? Can it offer a project for tomorrow? Only what will be accepted by collective recognition as a project designed to ensure the existence of the national community has future. And by ‘existence’ I mean not only a verbalized identity, but also the capacity to carry out necessary changes independently. The article presents the view that the Jagiellonian Idea does not rest on facts, but on an imagined picture of the one-time Rzeczpospolita. It presents a thesis about the connection between the flourishing of that state and the acceleration of transformations tied to the dialogic vortex generated by the Baltic-Black Sea axis of concentration. The failure of that project is ascribed to the changed circumstances, and perhaps to the insufficient energy elicited by this dialogic vortex. The experience of the Rzeczpospolita as a European project, in turn, indicates the road we may take today toward the completion of the transformation begun in 1989.
Echoes of the Jagiellonian Idea in the Present Polish Military Assistance Programs
Authors: Królikowski Hubert
Published: May 2018

Echoes of the Jagiellonian Idea in the Present Polish Military Assistance Programs

The exchange of ideas, views and mutual benefit from the experience of the traditions that prevailed in Central Europe in the Jagiellonian era also embraced the military area. Similarly, today the European Union, and especially NATO, unknowingly still refer to the Jagiellonian idea. It is certainly done by Poland, actively involved in the process of building a security and democracy zone in Central Europe. Actions called Military Assistance, which will be discussed in this article, are an important element of these activities in the area of security.
A crítica de Heidegger ao esquema sujeito-objeto
Authors: Siqueira Ana Carla de Abreu
Published: May 2018

Neste artigo, pretendemos avaliar como Martin Heidegger apresenta uma crítica ao esquema sujeito-objeto. Em um primeiro momento, explanamos o domínio do sujeito na época moderna. Para isso, discutimos o conceito na filosofia cartesiana. Em seguida, analisamos a relação entre sujeito e objeto, como também o método representativo. A intenção de Heidegger é apresentar uma nova maneira de pensar, com a qual podemos compreender os modos de ser dos entes e do próprio Dasein através da fenomenologia hermenêutica.
A linguagem como Weltansicht: a objetividade da compreensão hermenêutica
Authors: Da Silva Renata Ramos
Published: May 2018

Ao elucidar o caráter histórico da compreensão, na segunda parte de Verdade e Método, Gadamer contrapõem-se ao historicismo, uma vez que esse atribui uma pretensa objetividade às ciências humanas. A fim de defender a sua posição, o filósofo estabelece uma conexão entre os conceitos: história dos efeitos, consciência da história dos efeitos, mundo e linguagem. Tal conexão não é, contudo, realizada por mera justaposição destes, mas, ao contrário, por uma analogia entre os pares: história dos efeitos e consciência hermenêutica, por um lado, mundo e linguagem, por outro. Isto posto, pretendemos analisar a argumentação gadameriana em defesa do caráter hermenêutico da compreensão, mostrando que as razões para a consciência não objetivar a história são fundamentadas nas razões pelas quais o mundo não é objetivado na linguagem. Com isso, concluiremos que a visão gadameriana acerca da linguagem, assumindo um papel central na manutenção destas relações, é fundamental para a virada ontológica da hermenêutica.