bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Microenvironment Dynamics in Clear-Cell Renal Cell Carcinoma
Authors: Vuong Lynda , Kotecha Ritesh R. , Voss Martin H. , Hakimi A. Ari 
Published: September 2019

AbstractRenal cell carcinoma stands out as one of the most immune-infiltrated tumors in pan-cancer comparisons. Features of the tumor microenvironment heavily affect disease biology and may affect responses to systemic therapy. With evolving frontline options in the metastatic setting, several immune checkpoint blockade regimens have emerged as efficacious, and there is growing interest in characterizing features of tumor biology that can reproducibly prognosticate patients and/or predict the likelihood of their deriving therapeutic benefit. Herein, we review pertinent characteristics of the tumor microenvironment with dedicated attention to candidate prognostic and predictive signatures as well as possible targets for future drug development.Significance:Tumor microenvironment features broadly characterizing angiogenesis and inflammatory signatures have shown striking differences in response to immune checkpoint blockade and antiangiogenic agents. Integration of stromal and immune biomarkers may hence produce predictive and prognostic signatures to guide management with existing regimens as well as future drug development.
Blockade of β-Adrenergic Receptors Improves CD8+ T-cell Priming and Cancer Vaccine Efficacy
Authors: Daher Clara , Vimeux Lene , Stoeva Ralitsa , Peranzoni Elisa , Bismuth Georges , Wieduwild Elisabeth , Lucas Bruno , Donnadieu Emmanuel , Bercovici Nadège , Trautmann Alain , Feuillet Vincent 
Published: September 2019

Abstractβ-Adrenergic receptor (β-AR) signaling exerts protumoral effects by acting directly on tumor cells and angiogenesis. In addition, β-AR expression on immune cells affects their ability to mount antitumor immune responses. However, how β-AR signaling impinges antitumor immune responses is still unclear. Using a mouse model of vaccine-based immunotherapy, we showed that propranolol, a nonselective β-blocker, strongly improved the efficacy of an antitumor STxBE7 vaccine by enhancing the frequency of CD8+ T lymphocytes infiltrating the tumor (TIL). However, propranolol had no effect on the reactivity of CD8+ TILs, a result further strengthened by ex vivo experiments showing that these cells were insensitive to adrenaline- or noradrenaline-induced AR signaling. In contrast, naïve CD8+ T-cell activation was strongly inhibited by β-AR signaling, and the beneficial effect of propranolol mainly occurred during CD8+ T-cell priming in the tumor-draining lymph node. We also demonstrated that the differential sensitivity of naïve CD8+ T cells and CD8+ TILs to β-AR signaling was linked to a strong downregulation of β2-AR expression related to their activation status, since in vitro–activated CD8+ T cells behaved similarly to CD8+ TILs. These results revealed that β-AR signaling suppresses the initial priming phase of antitumor CD8+ T-cell responses, providing a rationale to use clinically available β-blockers in patients to improve cancer immunotherapies.
En quel sens la cité décrite au livre VII est-elle κατ᾽εὐχὴν, conforme au vœu de la science politique ?
Authors: Terrel Jean 
Published: September 2019

Abstract
In Politics VII, Aristotle not only gives us some general ideas on what makes a good city and the conditions of its implementation, but also provides a description of such a regime: 1. Citizenship is reserved for those whom, due to their natural attributes and sufficient wealth, may achieve political and ethical excellence; 2. In relation to their age, they are successively hoplites, citizens or priests. Therefore, all that remains to be examined is the relationship between such a regime and the “politeia”, which in the previous books (Politics IV-V) is the standard regarding cities whose citizens are rich, poor, or belong to the middle class.
Ideology and the Narrative of Climate Skepticism
Authors: Lejano Raul P. 
Published: September 2019

AbstractIt is reasonable to assume that more effective communication of climate science might be the remedy for widespread climate skepticism. However, narrative analysis of climate-skeptical discourse suggests it can be otherwise. Taking the United States as a case in point, we argue how at least some forms of climate skepticism are founded upon an ideological narrative that (for its adherents) is prior to, or more fundamental than, the issue of climate. In other words, skepticism may not always (or even usually) be fundamentally about climate to begin with. This more basic, universal, ideological construct at the root of climate skepticism encompasses social status, race and ethnicity, class, culture, and other social conditions. If climate-skeptical discourse in the United States is commonly built upon a genetic metanarrative that is really about social fracture, it may be resilient to scientific argument. It is quite possible that responding to climate skepticism will require addressing the more basic ideological divide and challenging the underlying genetic narrative. In the rest of the essay, we sketch out possible avenues for positive steps forward.
Defining and Managing the Preanalytical Phase With FMECA: Automation and/or “Human” Control
Authors: Bellini Claudia , Guerranti Roberto , Cinci Francesca , Milletti Eva , Scapellato Carlo 
Published: September 2019

Objective: Our scope is to provide methodological elements on how to manage effectively the preanalytical phase in the laboratory testing process, by objectively measuring the risk connected to the phases handled by man with respect to those managed by machines. Background: Preanalytical errors account for most of the mistakes related to laboratory testing and can affect patient care. Hence, it is necessary to manage the risk connected to the preanalytical phase, as required by certification and accreditation bodies. The risk assessment discloses the steps at greater risk and gives indications to make decisions. Method: We have reviewed the state of art in the automation of the preanalytical phase, addressing needs and problems. We have used the proactive risk assessment methodology FMECA (Failure Mode, Effects, and Criticality Analysis) to identify the most critical phases in our preanalytical process and have calculated the risk associated. Results: The most critical phases were the human controlled ones. In particular, the highest risk indexes were associated to manual acceptance of test orders, identification of the patients, tube labeling, and sample collection. Conclusion: Automation in the preanalytical phase is fundamental to replace, support, or extend the human contribution. Nevertheless each organization is different about workloads and competencies, so the most suitable management must be tailor-made in each context. Application: We present a method by which each organization is able to find its best balance between automation and human contribution in the control of the preanalytical phase.
Evaluation of the role of the colour tent in vision stimulation for children with complex disabilities and cerebral visual impairment: A feasibility study
Authors: Pilling Rachel Fiona , Little Suzanne Mary 
Published: September 2019

Children with profound and multiple disabilities commonly have their visual impairment overlooked when seeking to meet their complex health needs. The act of surrounding a child with little or no apparent visual function by a monochromatic translucent tent can serve to ‘switch on’ a child’s visual system. The aim of the project was to investigate the role of using colour tents to bring about attentional responses in children with complex disabilities including cerebral visual impairment. The evaluation comprises three phases, repeated on four occasions over the space of 4 weeks. The child’s visual attention prior to entering the tent and during the 5 minutes after leaving the tent was recorded. Moreover, the child’s responses and behaviours while in the tent were recorded. Nine children participated in the evaluation, mean age 6 years (range: 5–9 years). All children showed a change in visual behaviour on at least one occasion while in the colour tent. Most children required more than one session before a change in visual behaviour was noted. Only two children showed increase in visual awareness after any session, and there was no sustained effect demonstrated. This feasibility study has demonstrated that a short series of sessions in a colour tent is insufficient to demonstrate the effectiveness of a colour tent in stimulating visual awareness in children with complex needs. The methodology was acceptable to parents and teachers and lessons have been learned which will inform future studies.
Polymorphisms in the cytotoxic T lymphocyte-associated protein-4 immune regulatory gene and their impact on inhibitor development in patients with hemophilia A
Authors: Abdulqader Aveen M. Raouf , Mohammed Ali Ibrahim , Rachid Shwan 
Published: September 2019

Objective The development of inhibitors against infused factor VIII represents the most severe complication of substitution therapy in hemophilia A (HA) patients. Data on risk factors for inhibitor formation in Iraqi Kurdish patients with HA are unavailable. This study aimed to evaluate the impact of two single nucleotide polymorphisms (SNPs) in an immune regulatory gene in the emergence of inhibitors. Methods We focused on 126 patients with either severe or mild/moderate HA presenting with and without inhibitors. We analyzed the frequency of two polymorphisms in the cytotoxic T lymphocyte-associated protein-4 gene ( CTLA-4; CTLA-4-318C > T and CTLA-4 + 49A > G). Genotyping was performed using restriction fragment length polymorphism–PCR and direct sequencing. Results We found no significant correlation between the CTLA-4-318 C > T T allele and inhibitor development among patients with severe or mild/moderate HA. However, a significantly high inhibitor risk was detected for the CTLA-4 + 49 A > G G allele (odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.383–7.024) and (OR = 4, 95% CI = 1.719–9.437) among patients with severe and mild/moderate HA, respectively. Conclusion We conclude that the CTLA-4 +49 A > G SNP plays a substantial role as a potential risk determinant for inhibitor formation in Iraqi Kurdish patients with HA.
Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial
Authors: Diener Hans-Christoph , Goadsby Peter J , Ashina Messoud , Al-Karagholi Mohammad Al-Mahdi , Sinclair Alexandra , Mitsikostas Dimos , Magis Delphine , Pozo-Rosich Patricia , Irimia Sieira Pablo , Làinez Miguel JA , Gaul Charly , Silver Nicholas , Hoffmann Jan , Marin Juana , Liebler Eric , Ferrari Michel D 
Published: September 2019

Introduction Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. Methods This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6–8 hours apart). Results Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) ( p = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with ≥ 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p = 0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common. Conclusions Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The “sham” device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. Study identification and registration: PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844
Semi-Proletarianization in a Dual Economy: The Case of China
Authors: Qi Hao 
Published: September 2019

This paper proposes a model to explain the wage increase for migrant workers in China since the mid-2000s. First, the model consists of a capitalist sector and a non-capitalist sector. Second, households are semi-proletarianized because they participate in both family farming and wage production. Third, capitalist firms determine the wage level in order to extract labor. The paper demonstrates that semi-proletarianization is one of the three stages of the long-term dynamics of a dual economy like China. In so doing, it provides an alternative to the Lewis turning point literature. JEL Classification: B51, O53, E24
Concurrent participation in screening for cervical, breast, and bowel cancer in England
Authors: Rebolj Matejka , Parmar Dharmishta , Maroni Roberta , Blyuss Oleg , Duffy Stephen W 
Published: September 2019

Objectives To determine how many women participate in all three recommended cancer screening programmes (breast, cervical, and bowel). During their early 60s, English women receive an invitation from all the three programmes. Methods For 3060 women aged 60–65 included in an England-wide breast screening case–control study, we investigated the number of screening programmes they participated in during the last invitation round. Additionally, using the Fingertips database curated by Public Health England, we explored area-level correlations between participation in the three cancer screening programmes and various population characteristics for all 7014 English general practices with complete data. Results Of the 3060 women, 1086 (35%) participated in all three programmes, 1142 (37%) in two, 526 (17%) in one, and 306 (10%) in none. Participation in all three did not appear to be a random event ( p < 0.001). General practices from areas with less deprivation, with more patients who are carers or have chronic illnesses themselves, and with more patients satisfied with the provided service were significantly more likely to attain high coverage rates in all programmes. Conclusions Only a minority of English women is concurrently protected through all recommended cancer screening programmes. Future studies should consider why most women participate in some but not all recommended screening.
Part II: using an integrated case model for delivering mental health services in general practice for Pacific people
Authors: Mulder Roger , Sorensen Debbie , Kautoke Staverton , Jensen Seini 
Published: September 2019

Objective: To discuss an alternative model for delivering mental health services to Pacific people in general practice. Methods: Review of primary healthcare models which attempt to integrate behavioural healthcare with general practice. Results: There is some evidence that relationship-based collaborative models may improve both mental and physical health. Such a model has been implemented successfully by Alaskan Native Americans. Conclusion: An integrated model of healthcare incorporating Pacific cultural values may reduce stigma and improve engagement and efficacy in delivering mental health treatment to Pacific people, their families and communities.
Evaluation of an online cognitive behavioural therapy weight loss programme as an adjunct to anti-obesity medications and lifestyle interventions
Authors: Tham Marlene , Chong Terence WH 
Published: September 2019

Background and objectives: Obesity is a global pandemic with psychological, physical and metabolic consequences including in people with mental health conditions. Anti-obesity medications (AOMs) are available to treat obesity and can produce clinically meaningful weight loss but do not address associated psychological issues. We evaluated the usefulness and acceptability of an adjunct online cognitive behavioural therapy (CBT) programme for improving psychological outcomes. Method: We conducted a real-world 26-week observational study of 120 adults attending an obesity clinic who undertook a comprehensive weight management programme that included standard diet and exercise interventions, an AOM and an online 10-module CBT intervention. Baseline and 26-week psychological, metabolic and physical measures were compared. Results: At 26 weeks, depression, anxiety, stress and emotional eating levels for the sample decreased significantly compared to baseline (all p < .01). Satisfaction and acceptability were highly rated. The mean weight loss was 8.13 ± 3.83%. Mean waist circumference reduction was 7.62 ± 3.4 cm. Discussion: Online CBT has the potential to be a useful adjunct to AOMs and lifestyle interventions for providing psychological support as shown by improvement in mental health, emotional eating and acceptability scales. This warrants further investigation through a randomised controlled trial.
Pasifika Study Group: a child and adolescent mental health capacity building and leadership workshop with Pacific nations doctors and psychiatrists
Authors: Robertson Paul , Hagali Monica , Allen Myrielle , Leao-Tuitama George , Kowalenko Nick , Bush Allister 
Published: September 2019

Objective: To describe the Pasifika Study Group (PSG), a biennial workshop for Pacific nations psychiatrists and doctors working in psychiatry under the auspices of the Royal Australian and New Zealand College of Psychiatry Faculty of Child and Adolescent Psychiatry. Method: Since 2013 the PSG has brought together doctors and other health professionals from eight Pacific nations for a two-day study group. Results: On evaluation the PSG is considered informative and relevant and participants were generally confident of adapting the material to their own context. Conclusion: The PSG demonstrates a successful approach to regional engagement in mental health in the Pacific region.
CAMH in Primary Care Fiji: developing child and adolescent mental health in primary care
Authors: Robertson Paul , Paul Amaryah , Allen Myrielle 
Published: September 2019

Objective: To describe the CAMH in Primary Care Fiji Project. Methods: The context; process of development and planning; aims and goals; delivery and outcome are described. Results: Two CAMH in Primary Care Fiji training workshops were delivered in 2017 and 2018 with positive structured and unstructured feedback. Conclusion: A successful, collaboratively developed, culturally appropriate and replicable training for primary care in CAMH is possible.
Specialist Supportive Clinical Management for anorexia nervosa: what it is (and what it is not)
Authors: Jordan Jennifer , McIntosh Virginia VW , Bulik Cynthia M 
Published: September 2019

Objective: Specialist Supportive Clinical Management (SSCM) is a psychotherapy comprising a clinical management focus addressing anorexia nervosa (AN) symptoms and a supportive therapy component. SSCM has been an active control therapy in randomised controlled trials for AN, but has proven to be an effective therapy in its own right. There has been speculation about how this relatively straightforward therapy works. Some of the commentaries and descriptors used for SSCM, however, do not reflect the content or principles of SSCM. This paper clarifies areas of misunderstanding by describing what SSCM is and what it is not, particularly in relation to commentary about its constituent characteristics. Conclusions: SSCM utilises well established clinical management for AN (with a sustained focus on normalised eating and weight restoration) coupled with supportive therapy principles and strategies. Common factors across both arms include core counselling skills and a positive therapeutic alliance to promote adherence and retention in treatment for AN. Compared to other comparator therapies to date, SSCM is a simpler therapy without unique or novel theoretically derived strategies. Comparable outcomes with more complex psychotherapies raise the question of whether the combined core components of SSCM may be sufficient for many people with AN.
Being an Educator and Game Developer: The Role of Pedagogical Content Knowledge in Non-Commercial Serious Games Production
Authors: Linderoth Jonas , Sjöblom Björn 
Published: September 2019

Background and aim. Previous literature has discussed tensions between the field of game design and the field of education. It has been emphasized that it is important to address this tension when developing game based learning (GBL). In order to find potential ways of approaching this problem, we investigate the development of GBL when performed by those who have both pedagogical content knowledge (PCK) and experience in game development. Method. Two case studies about serious games production were conducted, a game section at a national defense college and a university course in educational game design. The cases, as well as individual development projects within the settings, were analyzed with a focus on the role of PCK during serious games development. Results. While the developers and instructors at the defence college, who designed games for their in-house needs, had both PCK and knowledge about game development, these competencies varied a lot among the participants at the university course. The results show that educational goals added complexity to the design process. By comparison, some studied game projects at the university course avoided this complexity. These projects legitimized their games as educational by suggesting unproven far transfer. In other cases, where the developers did have PCK, the instructional goals where taken as a starting point that guided the whole development process. This lead to games that were designed to match highly specific educational contexts. The developers, instructors and teachers in both of the settings who used their PCK tended to break a number of established game design heuristics that would have been counter productive in relation to the learning objectives of the games. Conclusions. The paper suggests that there is a need for people with pedagogical content knowledge AND knowledge about game development. Enhancing these dual competencies in game workers could forward the field of GBL.