bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROSPER: A phase III randomized study comparing perioperative nivolumab (nivo) versus observation in patients with localized renal cell carcinoma (RCC) undergoing nephrectomy (ECOG-ACRIN 8143).
Authors: Harshman Lauren Christine , Puligandla Maneka , Haas Naomi B. , Allaf Mohamad , Drake Charles G. , McDermott David F. , Signoretti Sabina , Cella David , Gupta Rajan T. , Shuch Brian M. , Choueiri Toni K. , Lara Primo , Kapoor Anil , Heng Daniel Yick Chin , Jewett Michael A.S. , Master Viraj A. , Michaelson M. Dror , Leibovich Bradley C. , Maskens Deb , Carducci Michael Anthony ,   On behalf of the PROSPER RCC Investigators
Published: March 2019

TPS684 Background: The anti-PD-1 antibody nivo improves overall survival in metastatic RCC and is well tolerated. There is no standard adjuvant systemic therapy that increases overall survival (OS) over surgery alone for non-metastatic RCC. Priming the immune system prior to surgery with anti-PD-1 has shown an OS benefit compared to a pure adjuvant approach in mouse solid tumor models. The PROSPER RCC trial aims to improve clinical outcomes by priming the immune system prior to nephrectomy with neoadjuvant nivo and continued engagement with adjuvant blockade in patients with high risk M0 RCC compared to surgery alone. Methods: This global, unblinded, phase 3 National Clinical Trials Network study is currently accruing patients with clinical stage ≥T2 or node positive M0 RCC of any histology. Tumor biopsy prior to randomization is mandatory to ensure RCC and permits in depth correlative science. The investigational arm will receive two doses of nivo 240mg prior to surgery followed by adjuvant nivo for 9 months (q2 wks x 3 mo followed by 480mg q4 wks x 6 mo). The control arm will undergo standard nephrectomy followed by observation. Randomized patients are stratified by clinical T stage, node positivity, and histology. To enhance accrual and patient quality of life, key upcoming amendments are being instituted. These include biopsy only in the nivo arm, allowance of oligometastatic disease and bilateral renal masses that can be fully resected/ablated, and change of nivo dosing to q4 wks (1 neoadj; 9 adj). With accrual of 766 patients, there is 84.2% power to detect a 14.4% absolute benefit in recurrence-free survival (RFS) at 5 years assuming the ASSURE historical control of ~56% to 70% (HR = 0.70). The study is also powered to evaluate a significant increase in overall survival (HR 0.67). Safety, feasibility, and quality of life endpoints critical to adjuvant therapy considerations are incorporated. PROSPER RCC embeds a wealth of translational work aimed at investigating the impact of the baseline immune milieu, the changes induced by neoadjuvant anti-PD-1 priming, and how both correlate with clinical outcomes. Clinical trial information: NCT03055013.
A phase II open-label study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pretreated with one immune-checkpoint inhibitor: The BREAKPOINT trial.
Authors: Verzoni Elena , Bearz Alessandra , De Giorgi Ugo , Nole Franco , Porta Camillo , Ratta Raffaele , Claps Melanie , Pagani Filippo , Martinetti Antonia , Cova Agata , Rivoltini Licia , De Braud Filippo G. , Procopio Giuseppe 
Published: March 2019

TPS685 Background: First-line treatment landscape of metastatic renal cell carcinoma (mRCC) is evolving with strong evidence in favour of PD-1/PD-L1 combinations over tyrosine kinase inhibitors (TKIs). No prospective data about efficacy of TKIs post immune-checkpoint inhibitor (CPI) combinations are available. Among TKIs, cabozantinib has demonstrated progression-free survival (PFS) and overall survival (OS) benefit over everolimus in pre-treated mRCC patients (pts). Methods: Overall 49 mRCC pts who received a previous CPI (anti PD-1/PD-L1) will be treated with cabozantinib. Pts will be stratified according to Heng prognostic group, duration of first-line and type of previous therapy received (CPI+CPI or CPI+TKI or CPI+anti-VEGF or CPI monotherapy). Key inclusion criteria include: one previous treatment with a PD-1/PD-L1 inhibitor in first-line and histological diagnosis of clear-cell RCC. The primary endpoint is to assess the efficacy of cabozantinib based on PFS. Secondary endpoints include evaluation of OS, objective response rate and safety profile of the drug. Exploratory endpoints include evaluation of PD-L1 levels by immunohistochemistry in tumor samples; the analysis of the immunological signature/profile of tumor cells; the state of circulating immune cells, as well as the modulating activity of cabozantinib on systemic tumor immunity; the evaluation of bone formation and reabsorption markers in pts with or without bone involvement. Cabozantinib will be administered orally at a dose of 60 mg/day continuously until evidence of disease progression or onset of unacceptable toxicity. Statistical design: By the methodology of Brookmeyer and Crowley, assuming an accrual period of 18 months and a minimum follow-up of 10 months (mos), 49 pts are necessary to detect an increment of the median PFS time from 3.8 mos to 7.4 mos with a power of 90% and one-sided alpha of 5%. The large sample critical value detecting the increment of the PFS median survival time will be 5.54 mos. To date, 2 pts have been enrolled. Clinical trial information: NCT03463681.
Lively Up Your Ontology
Authors: Marks Laura U. 
Published: March 2019

AbstractThis essay brings a process approach to the One-Many problem as treated in Gilles Deleuze’s thought, by focusing on the work of Ṣadr al-Dīn Muhammad al-Shīrāzī (Shiraz, 1571–1640). First acknowledging Avicenna’s concept of the univocity of being (attributed to John Duns Scotus) that influenced Deleuze, this essay examines how later Islamic philosophy, only recently transmitted to the West, provides methods for a lively process-based ontology. It compares Ṣadrā’s process cosmology to those of Gottfried Wilhelm von Leibniz and Alfred North Whitehead and examines his critique of abstraction in light of tashkīk, systematic ambiguity or modulation. The essay argues that Ṣadrā’s influence can make generative contributions to Deleuzean thought in terms of process realism, tashkīk as disjunctive synthesis, immanent causality, singularity, and an optimistic, world-oriented approach. Ṣadrā’s work allows us to rethink the boundary between philosophy and theology, and the essay proposes means to de-transcendentalize religious philosophy, if necessary.
Can a Dog Really Be a Man’s Best Friend?
Authors: Laqueur Thomas , Nehamas Alexander 
Published: March 2019

AbstractThis essay is an exchange between friends and scholars Thomas Laqueur and Alexander Nehamas. Laqueur offers a number of possible answers to the question “Why is a dog a man’s best friend?” as he explicates and analyzes a varied historical record of archaeological evidence, philosophy, art, and literature. Laqueur builds on Aristotle’s conception of friendship as he explores what types of friendships we humans have with dogs and how such relationships may benefit both species. Nehamas responds to Laqueur’s text and Aristotle on philia as he traces the limits of human relationships with dogs as well as human friends.
“A Picture of Peace”
Authors: Sato Courtney 
Published: March 2019

AbstractDuring the interwar period, internationalists declared Hawai‘i the “new Geneva” of the Pacific: a locus for regional diplomacy, social reform, and cross-cultural exchange. This article examines the Pan-Pacific Women’s Association (PPWA) as part of the emerging Honolulu-based Pan-Pacific internationalist movement. The PPWA enacted social reform grounded in ideals of antiracism, affective connection, and cross-cultural exchange. The article recuperates “friendship” in two ways: first, as a fundamental tenet of Pacific interwar internationalist praxis, and second, as an analytic attuned to internationalism’s entanglements with empire, race, gender, and sexuality. Despite the PPWA’s progressive antiracist liberal cosmopolitanism, the ideology and practice of international and interracial friendship often consolidated, rather than dismantled, hierarchies of race, nationality, class, gender, and sexuality.
The KRAB-zinc-finger protein ZFP708 mediates epigenetic repression at RMER19B retrotransposons
Authors: Seah Michelle K. Y. , Wang Yaju , Goy Pierre-Alexis , Loh Hui Mun , Peh Wen Jun , Low Diana H. P. , Han Brenda Y. , Wong Esther , Leong Ei Leen , Wolf Gernot , Mzoughi Slim , Wollmann Heike , Macfarlan Todd S. , Guccione Ernesto , Messerschmidt Daniel M. 
Published: March 2019

ABSTRACT
Global epigenetic reprogramming is vital to purge germ cell-specific epigenetic features to establish the totipotent state of the embryo. This process transpires to be carefully regulated and is not an undirected, radical erasure of parental epigenomes. The TRIM28 complex has been shown to be crucial in embryonic epigenetic reprogramming by regionally opposing DNA demethylation to preserve vital parental information to be inherited from germline to soma. Yet the DNA-binding factors guiding this complex to specific targets are largely unknown. Here, we uncover and characterize a novel, maternally expressed, TRIM28-interacting KRAB zinc-finger protein: ZFP708. It recruits the repressive TRIM28 complex to RMER19B retrotransposons to evoke regional heterochromatin formation. ZFP708 binding to these hitherto unknown TRIM28 targets is DNA methylation and H3K9me3 independent. ZFP708 mutant mice are viable and fertile, yet embryos fail to inherit and maintain DNA methylation at ZFP708 target sites. This can result in activation of RMER19B-adjacent genes, while ectopic expression of ZFP708 results in transcriptional repression. Finally, we describe the evolutionary conservation of ZFP708 in mice and rats, which is linked to the conserved presence of the targeted RMER19B retrotransposons in these species.
Review of Molecular Engineering for Horizontal Molecular Orientation in Organic Light-Emitting Devices
Authors: Watanabe Yuichiro , Sasabe Hisahiro , Kido Junji 
Published: March 2019

Abstract
Organic light-emitting devices (OLEDs) are widely used in next-generation eco-friendly solid-state display and lighting technologies. Most key optoelectronic functions of organic films used in organic semiconductor devices are dependent on two important factors: the electronic properties of single molecules, and the molecular orientations. The molecular orientation has recently attracted considerable attention, and been recognized as a crucial parameter for determining key optoelectronic functions of organic devices, such as device lifetime, efficiency, ionization potential, and carrier mobility of semiconductor amorphous films. In this review, we discuss horizontal molecular orientation from a molecular engineering perspective considering the three essential layers of OLEDs: the hole transport layer, electron transport layer, and emissive layer. In addition, we address the future challenges of next-generation OLED materials.
High-Intensity Aerobic Exercise Acutely Increases Brain-derived Neurotrophic Factor
Authors: ROSS RYAN E. , SALADIN MICHAEL E. , GEORGE MARK S. , GREGORY CHRIS M. 
Published: March 2019

ABSTRACT
Aerobic exercise (AEx) exerts antidepressant effects, although the neurobiological mechanisms underlying such effects are not well understood. Reduced brain-derived neurotrophic factor (BDNF) and elevated cortisol have been implicated in the pathophysiology of depression and appear to normalize with antidepressant treatment. Thus, BDNF and cortisol may serve as biological targets for developing AEx as an antidepressant treatment.

Purpose
This study examined the effects of AEx, of different intensities, on serum BDNF and cortisol in individuals with and without depression.

Methods
Thirteen participants with depression (10 females; age = 27.2 ± 6.9 yr; Montgomery–Äsberg Depression Rating Scale = 21.7 ± 4.7) and 13 control participants (10 females; age 27.2 ± 7.2 yr; Montgomery–Äsberg Depression Rating Scale = 0.5 ± 0.9) participated. Experimental visits consisted of 15 min of low-intensity cycling (LO) at 35% heart rate reserve, high-intensity cycling (HI) at 70% heart rate reserve, or sitting (CON). During each visit, blood samples were obtained at baseline, immediately postexercise (IP), and then every 15 min postexercise for 1 h (15P, 30P, 45P, and 60P). Group, condition, and time differences in BDNF and cortisol were assessed.

Results
There were no group differences in cortisol and BDNF. Secondary analysis revealed that BDNF increased in an intensity-dependent nature at IP, and cortisol was significantly elevated at 15P after HI. Changes in BDNF and cortisol showed significant linear relationships with changes in HR.

Conclusion
HI AEx can elicit acute, transient increases in BDNF and cortisol in young, healthy, and physically active, nondepressed and mild to moderately depressed individuals. This work suggests that AEx has potential to significantly affect the central nervous system function, and the magnitude of such effect may be directly driven by exercise intensity.
Comparison of auditory brainstem response and auditory steady state response audiometry by evaluating the hearing thresholds obtained in children with different severity of hearing loss
Authors: Aslam Muhammad Azeem , Javed Adeela , Moiz Abdul 
Published: March 2019

Objectives: To compare the hearing thresholds obtained with auditory brainstem response (ABR) and auditory steady state response (ASSR) audiometry in children with hearing loss.
Methods: Hearing thresholds were obtained by ABR and ASSR in children who presented with suspicion of deafness at Ear, nose & throat department of Al-Nafees Medical College Hospital Islamabad, between January to August 2018. The mean hearing thresholds obtained by two tests were compared within each category of severity of deafness. Time taken by both tests was also compared.
Results: A total of 57 patients (114 ears) were included in the study. Among them 27 (47.4%) were male and 30 (52.6%) were female. The mean age of patients at presentation was 42 months (±30.9) with age range from one to 12 years. Mean hearing thresholds obtained by click ABR, chirp ABR, ASSR (1, 2, 4 kHz) & ASSR (0.5, 1, 2, 4 kHz) was 56.25 (±27.61), 58.88 (±27.44), 58.03 (±21.26) & 56.35 (±22.86) respectively. Mean thresholds were comparable between click ABR & ASSR (1, 2, 4 kHz) and between chirp ABR & ASSR (0.5, 1, 2, 4 kHz) in all degrees of hearing loss categories except in those patients with normal hearing thresholds. The mean time taken by clicks ABR, chirp ABR and ASSR were four minutes seven seconds, three minutes 15 seconds and 16 minutes and 7 seconds respectively.
Conclusions: Hearing thresholds obtained by ABR and ASSR are comparable in all categories of severity of hearing loss. The time taken by ABR is less as compared to ASSR.
How to cite this:Aslam MA, Javed A, Moiz A. Comparison of auditory brainstem response and auditory steady state response audiometry by evaluating the hearing thresholds obtained in children with different severity of hearing loss. Pak J Med Sci. 2019;35(2):320-324. doi: https://doi.org/10.12669/pjms.35.2.688
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Efficacy of inverted internal limiting membrane flap for large idiopathic macular holes
Authors: Tayyab Haroon , Khan Asad Aslam , Jahangir Sana 
Published: March 2019

Objective: To evaluate the effectiveness of inverted internal limiting membrane flap in large idiopathic macular holes.
Methods: Twelve patients diagnosed with idiopathic macular holes larger than 400um underwent 23 gauge Pars Plana Vitrectomy (PPV) with inverted internal limiting flap and gas tamponade at Al-Ehsan Eye Welfare Eye Hospital, Lahore from February 2017 to February 2018. All cases were diagnosed on Spectral Domain Optical Coherence Tomography (SD-OCT) and were followed up for 6 months. At every follow-up, best corrected visual acuity and SD-OCT was done.
Results: We achieved macular hole closure in 91.6% (11/12) patients with idiopathic macular holes larger than 400um. Five out of 12 patients underwent combined phacoemulsification and PPV. One patient has flat hole closure which was considered failure. One patient was excluded from the study due to per-operative flap loss. This patient was not included in final data analysis of 12 patients. There was statistically significant gain in best corrected visual acuity after successful macular hole closure. We did not report any untoward events during or in the post-operative period.
Conclusion: Inverted internal limiting flap is an effective method for repairing large macular holes.
How to cite this:Tayyab H, Khan AA, Jahangir S. Efficacy of inverted internal limiting membrane flap for large idiopathic macular holes. Pak J Med Sci. 2019;35(2):315-319. doi: https://doi.org/10.12669/pjms.35.2.689
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Breathing and growth: Performing with plants
Authors: Arlander Annette 
Published: March 2019

Abstract
In this article breathing as a practice and vegetal growth as a form of movement are discussed by first returning to some repeated performances for camera made in Helsinki in 2004–05 and a text written in 2008 describing them in relation to Luce Irigaray’s ideas on breathing. These are then looked at from a current perspective and related to Michael Marder’s ideas on the place of plants, of growth as one of the Aristotelian forms of movement and Marder’s challenge to the arts to consider the vegetal. Based on Irigaray’s and Marder’s joint suggestion, in ‘Thinking anew’, to learn from plants, this article proposes that one way to begin considering performing with plants as a somatic practice could be, simply, breathing with plants.
The audience experience of immersion through intersubjective embodiment in Sensuous Geographies (2003)
Authors: Han Seok Jin 
Published: March 2019

Abstract
This article analyses an immersive interactive installation Sensuous Geographies (2003), created by choreographer Sarah Rubidge in collaboration with composer Alistair MacDonald. It applies phenomenological philosophies to critical interpretations of audience participants’ embodied experience. Rubidge employs choreographic sensibilities in designing a performative human–computer interface where the participants create their own sonic signature through physical behaviours while interacting with each other. The digital sound emerges as the ‘dys-appearing body’, as philosopher Drew Leder terms it, because it becomes part of their doubled embodiment but is perceptible due to its otherness. Moreover, the emergent sound embodies the participant’s subjectivity, which develops out of inter-subjectivity, since it is not transparent for the participant him/herself but generated through the intertwinement of the self and others. The self-perception of the corporeal body is heightened through digital imagery, costumes, facial veils and tactile materials, which provide the participant with a more intuitive and embodying experience of the sonic environment.
Fibromyalgia and the Feldenkrais method: Action research examining the teacher–student dynamic in transfer of learning
Authors: Fortin Sylvie , Hardy Élise 
Published: March 2019

Abstract
This action research brought together a group of Feldenkrais teachers and two groups of primarily female students living with fibromyalgia. The aim of the study was to work together to develop ways to allow the students to transfer knowledge acquired during weekly Feldenkrais lessons into their everyday lives. Based on the analysis of the empirical data collected, the research team developed a theoretical model of transfer of learning that calls attention to the importance of the student–teacher dynamic in the transfer of learning process. While this process may be different for each person, we argue that it occurs in three identifiable stages: (1) learning about the Feldenkrais method in the classroom; (2) applying the content and/or pedagogy of the Feldenkrais classes in everyday life; and (3) integrating knowledge gained through Feldenkrais classes into various spheres of one’s life. Despite the positive testimonies obtained throughout this action research, the authors of this article emphasize that the Feldenkrais method should not be seen as a panacea. Emphasis on the first-person experience, which is the basis of the Feldenkrais method, may run the risk of depoliticizing the broader social forces that contribute to the production and reproduction of fibromyalgia.
Shin Somatics contact unwinding: Developing mindfulness through interpersonal relationship
Authors: Purvis Denise 
Published: March 2019

Abstract
The Shin Somatics practice, contact unwinding, is a mindful improvisation practice aimed at clearing the chakras and promoting self-healing through physical and energetic connection of a primary mover and supportive guide. Developed by Sondra Fraleigh, contact unwinding encourages a primary mover to respond to internal cues, as well as a supportive guide’s energetic and tactile guidance. The practice is unique in encouraging partners to be present-centred, communicate clearly and honestly through touch, and reflect verbally in a manner allowing both parties to increase self-awareness without judgement or projection. This article explores contact unwinding’s potential to develop both mindfulness and interpersonal skills through holding presence and matching through touch. Using mindfulness-based cognitive behavioural therapy as an exemplar, I suggest the practice’s potential benefit to individuals seeking relief from psychosomatic disorders.
Between Rhetoric and Sophistry: The Puzzling Case of Plato’s Gorgias
Authors: Tusi Jacqueline 
Published: March 2019

AbstractThe case of Gorgias’ profession has been an object of ongoing dispute among scholars. This is mainly because in some dialogues Plato calls Gorgias a rhetorician, in others a sophist. The purpose of this article is to show that a solution only emerges in the Gorgias, where Plato presents Gorgias’ goals as a rhetorician and its associated arts. On this basis, Plato introduces a systematic division between genuine arts and fake arts, including rhetoric and sophistry, thereby identifying their conceptual differences and similarities. The paper concludes by arguing that Gorgias can be called both a rhetorician and a sophist, provided that the labeling is done from different perspectives.
Vertical integration approach for the intelligent Oil & Gas field
Authors: García Marcelo V. , Armentia Aintzane , Pérez Federico , Estévez Elisabet , Marcos Marga 
Published: March 2019

Abstract
The oil and gas industry envisions a smarter way of running their business where they can visualize their entire operation, call and retrieve production data effortlessly and seamlessly, collaborating across the entire enterprise to decrease production costs while increasing recovery. The so-called Intelligent Oil Field (IOF) promotes reference architectures and development approaches that improve the flexibility and efficiency of upstream and downstream process. In this sense, OPC UA provides local and remote access to plant information, allowing horizontal and vertical integration in a reliable, safe and efficient way. This article contributes an open IOF architecture for vertical integration based on cyber-physical production systems, configured under IEC 61499 and using OPC UA. Therefore, the proposal is suitable to achieve flexible manufacturing.