bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial
Authors: Klein Allan L , Lin David , Cremer Paul C , Nasir Saifullah , Luis Sushil Allen , Abbate Antonio , Ertel Andrew , LeWinter Martin , Beutler Anna , Fang Fang , Paolini John F 
Published: November 2020

ObjectiveRecurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated rilonacept efficacy and safety in RP.MethodsThis multicentre, open-label study enrolled adult patients with idiopathic or postpericardiotomy RP, symptomatic (≥2 pericarditis recurrences) or corticosteroid (CS) dependent (≥2 recurrences prior).Patients received rilonacept 320 mg SC load/160 mg SC weekly maintenance in a 6-week base treatment period (TP) followed by an optional 18-week on-treatment extension period (EP) (option to wean background therapy).ResultsOutcomes: pericarditis pain (numeric rating scale (NRS)) and inflammation (C reactive protein (CRP)) for symptomatic patients; disease activity after CS taper for CS-dependent patients. Secondary outcomes: health-related quality of life (HRQOL), pericarditis manifestations and additional medications. 25 unique patients enrolled, while 23 completed the EP (seven colchicine failures and five CS failures). In symptomatic patients, NRS and CRP decreased; response was observed after first rilonacept dose. NRS decreased from 4.5 at baseline to 0.7, and CRP decreased from 4.62 mg/dL at baseline to 0.38 mg/dL at end of TP. Median time to CRP normalisation: 9 days. Pericarditis manifestations resolved. 13 patients on CS at baseline completed the EP; 11 (84.6%) discontinued CS, and 2 tapered; CRP and NRS remained low without recurrence. Mean HRQOL scores improved in symptomatic patients. One serious adverse event (SAE) resulted in discontinuation of rilonacept.ConclusionsRilonacept led to rapid and sustained improvement in pain, inflammation (CRP and pericarditis manifestations) and HRQOL. CSs were successfully tapered or discontinued; safety was consistent with known rilonacept safety profile.Trial registration numberNCT03980522.
Investigation of the prognostic value of CD4 T cell subsets expanded from tumor-infiltrating lymphocytes of colorectal cancer liver metastases
Authors: Kroemer Marie , Turco Celia , Spehner Laurie , Viot Julien , Idirène Idir , Bouard Adeline , Renaude Elodie , Deschamps Marina , Godet Yann , Adotévi Olivier , Limat Samuel , Heyd Bruno , Jary Marine , Loyon Romain , Borg Christophe 
Published: November 2020

BackgroundThe positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells.MethodsLiver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients’ clinical outcomes.ResultsWe successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3lowcultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007).ConclusionsOur data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients’ survival, suggesting a particular role of this T cell subset in CRC immune contexture.Trial registration numberNCT02817178.
Wrinkle in the plan: miR-34a-5p impacts chemokine signaling by modulating CXCL10/CXCL11/CXCR3-axis in CD4+, CD8+T cells, and M1 macrophages
Authors: Hart Martin , Nickl Laura , Walch-Rueckheim Barbara , Krammes Lena , Rheinheimer Stefanie , Diener Caroline , Taenzer Tanja , Kehl Tim , Sester Martina , Lenhof Hans-Peter , Keller Andreas , Meese Eckart 
Published: November 2020

BackgroundIn 2016 the first-in-human phase I study of a miRNA-based cancer therapy with a liposomal mimic of microRNA-34a-5p (miR-34a-5p) was closed due to five immune related serious adverse events (SAEs) resulting in four patient deaths. For future applications of miRNA mimics in cancer therapy it is mandatory to unravel the miRNA effects both on the tumor tissue and on immune cells. Here, we set out to analyze the impact of miR-34a-5p over-expression on the CXCL10/CXCL11/CXCR3 axis, which is central for the development of an effective cancer control.MethodsWe performed a whole genome expression analysis of miR-34a-5p transfected M1 macrophages followed by an over-representation and a protein–protein network analysis. In-silico miRNA target prediction and dual luciferase assays were used for target identification and verification. Target genes involved in chemokine signaling were functionally analyzed in M1 macrophages, CD4+and CD8+T cells.ResultsA whole genome expression analysis of M1 macrophages with induced miR-34a-5p over-expression revealed an interaction network of downregulated target mRNAs includingCXCL10andCXCL11.In-silico target prediction in combination with dual luciferase assays identified direct binding of miR-34a-5p to the 3′UTRs ofCXCL10andCXCL11. Decreased CXCL10 and CXCL11 secretion was shown on the endogenous protein level and in the supernatant of miR-34a-5p transfected and activated M1 macrophages. To complete the analysis of the CXCL10/CXCL11/CXCR3 axis, we activated miR-34a-5p transfected CD4+and CD8+T cells by PMA/Ionomycin and found reduced levels of endogenous CXCR3 and CXCR3 on the cell surface.ConclusionsMiR-34a-5p mimic administered by intravenous administration will likely not only be up-taken by the tumor cells but also by the immune cells. Our results indicate that miR-34a-5p over-expression leads in M1 macrophages to a reduced secretion of CXCL10 and CXCL11 chemokines and in CD4+and CD8+T cells to a reduced expression of CXCR3. As a result, less immune cells will be attracted to the tumor site. Furthermore, high levels of miR-34a-5p in naive CD4+T cells can in turn hinder Th1 cell polarization through the downregulation of CXCR3 leading to a less pronounced activation of cytotoxic T lymphocytes, natural killer, and natural killer T cells and possibly contributing to lymphocytopenia.
A patient-oriented approach to the development of a primary care physical activity screen for embedding into electronic medical records
Authors: Clark Rebecca E. , Milligan James , Ashe Maureen C. , Faulkner Guy , Canfield Carolyn , Funnell Larry , Brien Sheila , Butt Debra A. , Mehan Upender , Samson Kevin , Papaioannou Alexandra , Giangregorio Lora 
Published: November 2020

Physical activity questionnaires exist, but effective implementation in primary care remains an issue. We sought to develop a physical activity screen (PAS) for electronic medical record (EMR) integration by 1) identifying healthcare professionals’ (HCPs), patients’ and stakeholders’ barriers to and preferences for physical activity counselling in primary care; and 2) using the information to co-create the PAS. We conducted semi-structured interviews with primary care HCPs, patients and stakeholders, and used content and thematic analyses to inform iterative co-design of the PAS. Interviews with 38 participants (mean age 41 years) resulted in 2 themes: 1) HCPs are willing to conduct physical activity screening, but acknowledge they don’t do it well; and 2) HCPs have limited opportunity and capacity to discuss physical activity, and need a streamlined process for EMR that goes beyond quantifying physical activity. HCPs, patients and stakeholders co-designed a physical activity screen for integration into the EMR that can be tested for feasibility and effects on HCP behaviour and patients’ physical activity levels. Novelty: EMR-integration of physical activity screening needs to go beyond just asking about physical activity minutes. Primary care professionals have variable knowledge and time, and need physical activity counselling prompts and resources. We co-developed a physical activity EMR tool with patients and primary care providers.
Fluctuating viscoelasticity based on a finite number of dumbbells
Authors: Hütter Markus , Olmsted Peter D. , Read Daniel J. 
Published: November 2020

Abstract.Two alternative routes are taken to derive, on the basis of the dynamics of a finite number of dumbbells, viscoelasticity in terms of a conformation tensor with fluctuations. The first route is a direct approach using stochastic calculus only, and it serves as a benchmark for the second route, which is guided by thermodynamic principles. In the latter, the Helmholtz free energy and a generalized relaxation tensor play a key role. It is shown that the results of the two routes agree only if a finite-size contribution to the Helmholtz free energy of the conformation tensor is taken into account. Using statistical mechanics, this finite-size contribution is derived explicitly in this paper for a large class of models; this contribution is non-zero whenever the number of dumbbells in the volume of observation is finite. It is noted that the generalized relaxation tensor for the conformation tensor does not need any finite-size correction.Graphical abstract
Cyclic quantum teleportation via GHZ-like state
Authors: Verma Vikram 
Published: November 2020

Following the work of Chen et al. [Quantum Inf. Process. 16, 201 (2017)] and Zhang [Mod. Phys. Lett. A 34, 1950290 (2019)], we propose a scheme for cyclic quantum teleportation (CYQT) in which three participants Alice, Bob and Charlie can teleport three arbitrary single-qubit information states cyclically among themselves by using GHZ-like states. Chen et al. and Zhang proposed schemes for CYQT and bidirectional quantum teleportation (BQT) involving three participants, respectively. In the scheme of Chen et al., the quantum teleportation (QT) can be realized successfully between any two participants without the help of third participants and in Zhang’s scheme, two unknown single-qubit states are teleported bidirectionally between two participants with the help of a third participant. On the other hand, in our proposed scheme, all the three participants are controller as well as sender and receiver. The teleportation processes Alice [Formula: see text] Bob, Bob [Formula: see text] Charlie and Charlie [Formula: see text] Alice are controlled by Charlie, Alice and Bob, respectively, and hence the CYQT could not be realized successfully without the cooperation of all three participants. If any one participant denies to cooperate with other two participants, then the CYQT cannot be realized successfully.
Does holographic equipartition demand a pure cosmological constant?
Authors: Krishna P. B. , Mathew Titus K. 
Published: November 2020

The spacial expansion of the universe could be described as a tendency for satisfying holographic equipartition which inevitably demands the presence of dark energy. We explore whether this novel idea proposed by Padmanabhan gives any additional insights into the nature of dark energy. In particular, we obtain the constraints imposed by the law of emergence on the equation of state parameter, [Formula: see text]. We also present a thermodynamic motivation for the obtained constraints on [Formula: see text]. Further, we explicitly prove the feasibility of describing a dynamic dark energy model through the law of emergence. Interestingly, both holographic equipartition and the entropy maximization demand an asymptotically de Sitter universe with [Formula: see text], rather than a pure cosmological constant.
A modern guide to 𝜃-Poincaré
Authors: Addazi Andrea , Marcianò Antonino 
Published: November 2020

Motivated by the recent interest in underground experiments phenomenology (see Refs. 1–3), we review the main aspects of one specific noncommutative space–time model, based on the Groenewold–Moyal plane algebra, the [Formula: see text]-Poincaré space–time. In the [Formula: see text]-Poincaré scenario, the Lorentz co-algebra is deformed introducing a noncommutativity of space–time coordinates. In such a theory, a new quantum field theory in noncommutative space–time can be reformulated. Tackling on several conceptual misunderstanding and technical mistakes in the literature, we will focus on several issues such: (i) the construction of fields theories in [Formula: see text]-Poincaré; (ii) the unitarity of the S-matrix; (iii) the violation of locality, (iv) the violation of the spin-statistic theorem and the Pauli principle; (v) the observables for underground experiments.
Robust control and optimized parallel control double loop design for mobile robot
Authors: Abougarair Ahmed J. , Elmolihi Ali S. 
Published: November 2020

Robots have been used in many applications in the past few decades. Moreover, due to high nonlinearity behavior of these systems, an optimal and robust control design approaches have been considered to stabilize and improve their performance and robustness. The uncertainties of the time delay on the output states of the mobile robot system have a significant influence on the system nominal performance. As a result, the work becomes here to address the influence of these uncertainties on the robot system performance. In order to achieve this objective, the nonlinear controller via sliding mode control (SMC) is designed by selecting a suitable sliding surface dynamics in which the considered robot displacement and tilt angle are sliding on. The lyapunov function is considered here to accomplish the design of the sliding control signals for robot stabilization. Furthermore, the stability of the considered system is guaranteed due to convergence of the lyapunov functions into zero when the state trajectories tend to desired set points. In addition, we consider the trajectory tracking and stabilization of TWBMR system using parallel double loop PID controllers whose controllers gains are tuning via linear quadratic regulator (LQR) approach. Finally, to demonstrate the effectiveness of SMC and PID-LQR design methods, the comparison is carried out when the nominal and uncertain conditions.
A Future in Ruins
Authors: Jorritsma Jilt 
Published: November 2020

Abstract
Around the world, the rise of temperatures due to global warming is revealing and exposing forgotten traces of the past that are still scored somewhere in the physical terrain. This paper suggests that the transformative landscapes of the Anthropocene not only confront our present world with a ruined and unprecedented future; they also draw our attention to suppressed and stowed-away memories and geographies from the past. By examining imaginaries of sustainable futures in Mexico City, New York and Amsterdam, it will be shown that site-specific ruins and traces of past realities have an evocative potential: they are used to imagine alternative historical trajectories and indicate possible alternative futures that challenge the absoluteness of our present world. The underlying temporality in these imaginaries is one in which the future is portended as a return of a past: there lies a future in these ruins.
Subjective Passage of Time during the Pandemic: Routine, Boredom, and Memory
Authors: Wittmann Marc 
Published: November 2020

Abstract
Over the weeks of social isolation during the COVID-19 pandemic, people typically reported that time had passed comparably quickly. Although time might have passed slowly during moments of anxiety and boredom for some, many felt a speeding up of the passing days and weeks. Here I attempt to explain the experience of time during the pandemic with cognitive models of time perception as related to the present moment (prospective time) and in hindsight (retrospective time). Retrospective judgments of time intervals rely on memory traces. The more contextual changes experienced during a given time interval, the longer duration is judged when looking back over past time intervals. More routine activities, as experienced by many during the pandemic, even when under time pressure, lead to fewer memorable events stored in autobiographical memory. This creates the impression that time has passed considerably more quickly.
Eastern-Western Women’s Self-Concept
Authors: Ohebshalom Nicole 
Published: November 2020

Abstract
Although cross-cultural influences on human behavior have been the subject of many scholarly works, few studies have focused on the life experiences of women from hyphenated cultural identities and how these experiences inform a woman’s view of herself as a sexual being, in particular, the influence of cross-cultural experiences on women with combined Western and Eastern culture references. This study analyzes four interviews with first-generation Israeli-Iranian women, who describe how their sexual self-concepts evolved as a result of living between both cultures, in the “space of the hyphen.” I used the Listening Guide methodology to inform the interviews and the data analysis, which reveal the influence of family power, patriarchal social practices, and the women’s desire to distinguish themselves from cultural norms. It introduces multilayered views and processes associated with each woman’s outlook of her evolving sexual self-concept.
International Law in the Buffer
Authors: Burke Róisín 
Published: November 2020

Abstract
Territorial disputes historically have been commonplace in the Transcaucasian region. Nagorno-Karabakh is a region legally recognised as a part of Azerbaijan, but has historically been disputed by Armenia and Azerbaijan. It was an autonomous region during Soviet times, but fell within the administrative boundaries of the then Soviet Republic of Azerbaijan. Nagorno-Karabakh has operated de facto independently since 1992, when it declared independence. Azerbaijanis from regions bordering Nagorno-Karabakh were displaced from their homes in the 1990s. This created what some refer to a security buffer, but which constitute occupied territory. Azerbaijan seeks the return of all territories. For Karabakh Armenians any dispute settlement that would leave Nagorno-Karabakh within Azerbaijan is untenable, given security threats. The conflict is coloured by history, past injustices, and ideologies around identity. Despite decades of mediation attempts by the osce and others, the territory remains fervently disputed. Border skirmishes have been frequent since the 1990s. However, since September 2020 serious escalations in hostilities and violence in region risk a broader regional conflict and drawing in Turkey, Russia and Iran. The paper provides a historical exposition of factors underpinning the dispute, which are critical to understanding its context and ultimate resolution. It examines the claim to self-determination by the people of Nagorno-Karabakh from the perspective of international law. It addresses the interplay between conflicting norms of territorial integrity and self-determination. The paper reflects on questions of statehood, and on the emerging concept of remedial secession in cases of egregious human rights violations and where internal self-determination is denied, and their possible relevance to the Nagorno-Karabakh dispute.
Cybercultural Transgressions in Comments by Iranian Instagram Users
Authors: Oskuie Shalaleh Meraji , Mohamadkhani (corresponding author) Kamran , Delavar Ali , Farhangi Ali Akbar 
Published: November 2020

Abstract
The ease of communication and anonymity that computer-mediated communication provides has created fertile ground for transgressive (socially non-normative) online behaviours. The purpose of the current research is to explore the types of transgressive comments on Iranian celebrities’ Instagram pages. Within a qualitative descriptive approach, the current research employs Braun and Clarke’s ‘thematic analysis’ to analyze transgressive user comments. Using a judgmental (purposive) non-probability sampling technique, we selected posts from 22 Iranian celebrities’ Instagram pages. Afterwards, we analyzed 53,066 comments in these posts and extracted four dominant transgressive themes: ‘unwanted advertisement,’ ‘partner seeking,’ ‘attention seeking,’ and ‘emotional release’; we then extracted their sub-themes.
Transgressive behaviours disrupt the communicative experience on social networks, endanger users’ security and safety, and can lead to mental problems and even offline harassment and violence. Recognizing these behaviours and their patterns can contribute to more effective use of social control means.
Digital Technology, Physical Space, and the Notion of Belonging among Chinese Migrants in Japan
Authors: Wang Xinyu (Promio) 
Published: November 2020

Abstract
This paper illustrates how, among Chinese migrants in Japan, the notion of belonging is constructed and modified by their use of digital technology, by presenting digital technologies as a continuum of physical and digitized life experiences.
Drawing on interviews with 55 Chinese migrants in Japan, this paper argues that Chinese migrants are increasingly engaged in digital spaces that combine the online and offline and permit their presence at a transnational scale, through a collectively imagined ‘Chinese’ identity. However, because of the influence of physical spaces on Chinese migrants’ transnational, diasporic experiences, this transnational engagement does not lead to the construction of a transnational or a relatively static nation-state sense of belonging. Instead, for Chinese migrants in Japan, the notion of belonging can be based on the situation and context, and it can switch between the home and host countries.
Textual Criticism and Its Impact on the Study of Israel’s Religion and Hebrew Grammar
Authors: Torijano Pablo A. 
Published: November 2020

Abstract
Textual criticism is a necessary first step when studying a biblical text. However, textual issues go beyond isolated readings and reach the literary composition of the book, Hebrew grammar, theology or history. The books of Kings / Kingdoms offer many examples where textual variants solve difficulties or shed light on other venues of study. In the present article, we study the name Molek / Molok / Milkom, the presence of the proleptic pronoun in some verses of Kings, and the names with suffix -ay from a textual point of view.