bluuebunny/crossref_metadata_2025_split huggingface dataset:
57. CIRCULATING TUMOR CELLS (CTC) IN CEREBROSPINAL FLUID (CSF) AS A PREDICTOR OF SURVIVAL IN CNS METASTASES
Authors: Diaz Maria , Singh Priya , Kotchekov Ivan , Skakodub Anna , Reiner Anne , Panageas Katherine , Ramanathan Lakshmi , Pentsova Elena 
Published: August 2020

Abstract

BACKGROUND
CSF-CTC testing using the CellSearch® platform is a validated diagnostic tool for leptomeningeal metastases (LM) from solid tumors. CSF-CTCs can also be detected in patients with brain metastases (BM), but their significance is unclear. Our objective was to evaluate the utility of CSF-CTC measurement in predicting outcomes in CNS metastases.

METHODS
We conducted a retrospective single-institution review of patients who underwent CSF-CTC testing from 2016–2019. Information on neuroaxis imaging, CSF results, systemic cancer status, tumor molecular profile and survival was collected. LM was diagnosed by unequivocal MRI findings and/or positive or suspicious CSF cytology. Survival analyses were performed using Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identified through recursive partitioning analysis.

RESULTS
A total of 407 patients (38% lung primary, 34% breast, 28% other tumor types) were included; of these, 144 had LM and 233 had BM diagnosed before or around the time of CSF analysis (97 had both). We identified a subgroup of newly diagnosed CNS metastases, comprising 144 patients with LM, BM, or both diagnosed within 30 days of CSF sampling: 70 patients with LM, 43 with BM, and 31 with both. For 101 patients with newly diagnosed LM, mean and median CSF-CTCs were 127.3 and 200, respectively, compared to 44.6 and 0 in the overall cohort; 73/101 had positive (66) or suspicious (7) cytology. CSF-CTCs predicted survival in patients with newly diagnosed LM, with optimal cutoff identified at 61 CSF-CTCs, above which the risk of death doubled (HR=2.09, 95% CI: 1.13–3.87, p=0.02). For this group, positive/suspicious cytology was also associated with higher risk of death, but this result was not statistically significant (HR=1.79, 95% CI: 0.95–3.35, p=0.07).

CONCLUSION
In newly diagnosed LM, quantification of CSF-CTCs predicts survival. CSF-CTC measurement can be used as a prognostic tool in patients with CNS metastases.
65. INVASIVE HISTOPATHOLOGY DRIVES POOR OUTCOMES IN SURGICALLY RESECTED BRAIN METASTASES
Authors: Dankner Matthew , Caron Maxime , Al-Saadi Tariq , Yu WenQing , Ouellet Veronique , Uyen Le Phuong , Ezzeddine Rima , Neubarth Noah , Savage Paul , Zuo Dongmei , Altoukhi Huda , Bourque Guillaume , Ragoussis Jiannis , Diaz Roberto , Park Morag , Guiot Marie-Christine , Lam Stephanie , Petrecca Kevin , Siegel Peter M 
Published: August 2020

Abstract

BACKGROUND
Brain metastasis (BrM) patients treated with surgery and radiotherapy frequently experience local recurrence (LR), leptomeningeal metastasis (LM), and poor overall survival (OS). We sought to correlate the presence of invasive or circumscribed histopathological growth pattern, observed in the BrM lesion and surrounding brain, with these outcomes, and to study molecular mediators of parenchymal invasion.

METHODS
We assessed the HGP of H&E-stained slides from 164 surgically resected BrM from 147 patients. HGP was correlated with incidence of LR, LM and OS. Single-cell RNA sequencing (scRNAseq) was performed on three invasive HGP patients, sampling the metastasis center (MC) and surrounding brain (SB) outside of the contrast-enhancing region. Orthotopic patient-derived xenograft models (OPDX) were established from N=30 brain metastasis via intracranial propagation.

RESULTS
56/164 BrM specimens (34%) showed a circumscribed growth pattern between the tumor and adjacent brain (cHGP) while 108/164 (66%) showed significant invasion of tumor lobules or single cells into the brain parenchyma (iHGP). iHGP was associated with LR, LM and shortened OS in BrM patients. OPDX models of BrM retain features of patient BrM, including HGP. scRNAseq identified abundant cancer cells in SB that overexpressed a number of genes involved in cell survival, invasion and metastasis compared to matched cancer cells in MC. Validation of these targets with immunohistochemistry in patient and OPDX tissues revealed cold-inducible RNA binding protein (CIRBP) overexpression in iHGP patient and OPDX BrM. Modulation of CIRBP expression in OPDX and cell line models of iHGP BrM delayed BrM progression and extended OS.

CONCLUSION
iHGP is a poor prognostic indicator in patients with surgically resected BrM, establishing HGP as an important prognostic factor that should be considered by clinicians treating BrM patients. We identify CIRBP as a functional mediator of this process.
67. INCREASED RISK OF BREAST CANCER BRAIN METASTASIS WITH EGFR AND Ki-67 EXPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Job Arun , Hulsbergen Alexander , Jhun Ray , Jessurun Charissa , Smith Timothy , Broekman Marike 
Published: August 2020

Abstract

PURPOSE
This study aims to conduct a systematic review of the literature to identify biomarkers associated with breast cancer brain metastasis (BCBM).

METHODS
A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane for relevant literature up until October 1, 2018. Case reports, conference abstracts, and expert opinions/letters were excluded. Studies were included if they investigated risk factors for BCBM in a cohort of patients with locoregional or metastatic breast cancer of any subtype.

RESULTS
From the 4866 studies that were screened, 117 were selected for inclusion and review. Twenty-eight unique biomarkers were investigated, of which three (EGFR, Ki-67, and p53) were assessed by more than two authors. In a pooled analysis of 3 studies, EGFR expression was associated with an increased risk of BM (RR 3.48, 95% CI 2.27–5.32, I2=0%, p-interaction = 0.39, n= 571 patients). In a pooled analysis of 5 studies, increased Ki-67 expression was associated with an increased risk of BM (RR 2.91, 95% CI 1.96–4.32, I2=59%, p-interaction = 0.05, n= 1,178). In a pooled analysis of 4 studies, p53 expression was not associated with a statistically significant risk of BM (RR 1.42, 95% CI 0.98–2.06, I2=53%, p-interaction = 0.10, n= 738).

CONCLUSION
This study summarizes the various biomarkers investigated for a role in breast cancer brain metastasis. Two biomarkers, EGFR and Ki-67 were identified as having a statistically significant increased risk of BCBM while p53 was not found to be statistically significant. Future studies are needed to develop more robust prediction models, as well as evaluate the other biomarkers identified in this study, which could help clinicians identify patients at high risk of breast cancer brain metastasis.
69. PERMANENT INTRACAVITARY Cs131 BRACHYTHERAPY FOR PREVIOUSLY-IRRADIATED RECURRENT BRAIN METASTASES: INITIAL CLINICAL AND RADIATION SAFETY EXPERIENCE
Authors: Moss Nelson S , Imber Brandon S , Prasad Kavya , Chu Bae P , Goel Arun , Aramburu-Nunez David , Bellamy Michael , Yang T Jonathan , Khan Atif J , Dauer Laurence T , Cohen Gilad N , Beal Kathryn , Tabar Viviane 
Published: August 2020

Abstract

OBJECTIVE
Recurrence of previously-irradiated brain metastases (BrM) presents a significant challenge. We describe our initial experience using salvage resection with Cs131 brachytherapy in previously-irradiated BrM.

METHODS
Between September 2019 and April 2020, 9 patients with recurrent BrM underwent maximally-safe metastatectomy. Following pathological confirmation of viable recurrence, cavities were implanted with permanent Cs131 brachytherapy (GammaTile, GT Medical Technologies). Prescribed dose was 60Gy at 5mm from the cavity. Postimplant dosimetry (V100) was calculated on postoperative day 1 fused CT/MRI. Intraoperative team exposure was recorded using intraoperative ring dosimetry, and patient dose-rates measured postoperatively informed patient, family and medical-staff exposure modeling.

RESULTS
Nine patients (55% female, median age 54) underwent 10 implantations (6 supratentorial, 4 infratentorial). Median preoperative maximum diameter was 3.5cm (2.3–6.3) and histologies included breast, gastrointestinal, lung, kidney and oral cavity squamous cell carcinomas. Five had undergone prior resection or laser ablation. All lesions received &gt;/=1 prior course of stereotactic irradiation a median of 10.1 months (3.7–15.9) earlier. Eight lesions were gross-totally resected. Median number of implanted Cs131 seeds was 16 (12–28) with median seed strength of 61.8U (42.4–98.0). Median postoperative cavity size was well-correlated with the number of implanted seeds (Pearson R=0.75, p=0.03). Median V100 dose coverage of the cavities and uniform 5mm expansion of the cavities were 99% (79–100%) and 79% (51–95%), respectively. Median measured exposure rates were 90mR/hr (28–152) on contact, 9.15mR/hr (2.7–13.9) at 30cm and 1.4mR/hr (0.6–2.3) at 1 meter from the patient. Mean ring dose was 6.83mrem (0–18) for the radiation oncologist and 9.17mrem (0–15) for the neurosurgeon. Modeled lifetime family-member and visitor exposure was 116mrem (52-193mrem), and healthcare worker exposure was 39mrem (17-64mrem), all well below regulatory limits. There were no immediate wound complications or unanticipated neurologic injuries.

CONCLUSION
In our early experience, salvage interstitial Cs131 implantation was safely employed for recurrent brain metastases.
Emmanuel Levinas
Authors: Katz Claire 
Published: August 2020

Emmanuel Levinas (b. 1906–d. 1995) was a French-Jewish thinker known primarily as the philosopher of the ‘other.’ He studied with Husserl and Heidegger in the 1920s. He introduced phenomenology to France through his translation of Husserl’s Cartesian Meditations into French, and he developed a lifelong friendship with Maurice Blanchot. Prior to the rise of Hitler and Nazi Germany, Levinas’s philosophical work focused on Husserlian phenomenology. His thought took a dramatic turn in the mid-1930s when he focused on the philosophical threat of Nazism. He spent 1940–1945 in a German POW camp. Returning to Paris after the war, he immediately went back to work for the Alliance Israélite Universelle (AIU), where he became director of the École Normale Israélite Orientale (Enio), the Jewish day school. He resumed working on his question from the 1930s—the philosophical problem of identity and transcendence—with an added urgency in the wake of World War II. From 1946 until his death in 1995, Levinas’s ethical project searched for a way to address this philosophical problem of escape, developing a view of the self as an ethical subject that allows one to transcend the self without leaving the body behind. From the 1940s to the early 1960s, he developed the first version of his ethical project. In the late 1960s and early 1970s, he responded to criticisms of that early work. Central to Levinas’s description of the ethical relationship are references to literary works including Dostoyevsky and Shakespeare. Although Levinas was an observant Jew, the biblical narratives, in addition to being part of a sacred text, also serve as rich sources of examples for the philosophical descriptions of the ethical relationship he develops. Levinas is not obviously identified with literary theory—not in the way that Derrida is, for example. He did become popular within literary theory circles in the 1990s and might be taught more frequently in comparative literature departments than in philosophy departments, especially in the United States. His friendship with both Blanchot and Derrida had a significant impact not only on their thinking but also those who whose work was influenced by them. References to terms like the other/Other, the trace, hospitality, ethics, and alterity found throughout Blanchot and Derrida, and now more commonly in literary theory, can be traced back to Levinas’s ethical project.
Kenzo Tange
Authors: Lin Zhongjie 
Published: August 2020

Kenzo Tange (Tange Kenzō, b. 1913–d. 2005) was arguably the most prominent Japanese architect in the 20th century. His long career had been tied to the changing trajectory of the nation, making him an important cultural figure to study in modern Japan. Inspired by Le Corbusier since his youth, Tange followed modernism throughout his career with strong faith in its rational order, technological power, and universalizing values, yet he always tried to incorporate them with a Japanese identity and aesthetics. The triumphs in two open design competitions sponsored by the wartime militarist government lifted him to the national stage at a young age but have remained controversial since. He emerged again as the leader during the country’s postwar resurrection and economic takeoff and designed a series of national projects, including the Hiroshima Peace Memorial Park, the Tokyo City Hall, and the National Olympic Gymnasiums, and led the team in the planning and design for the 1970 World Expositions in Osaka. Japan’s continuing growth of economic power in the 1970s through 1990s sent him all over the world with large-scale designs in Macedonia, Italy, Singapore, Middle East, Africa, and the United States, among other nations. Tange was also an influential urbanist, an aspect that has in the early 21st century drawn greater interest of scholarship. His seminal work of city design was the 1960 Plan for Tokyo, which articulated a spectacular though incremental expansion of a linear megastructure cross the Tokyo Bay to carry a new city of five million to decentralize the overcrowded metropolis and basically influenced all his ensuing attempts of inventing inclusive urban frameworks for the transforming postindustrial cities. This endeavor was shared by the architects of Metabolism, who launched the avant-garde movement that Tange helped flourish in the 1960s. Tange’s collaborations with artists, critics, and photographers, as well as his constant engagement in global intellectual exchanges, also generated rich outcomes and served his aspiration for Japan’s cultural identity and international influence, manifest in his coauthored accounts on the Katsura Villa and Ise Shrine, respectively, as well as in Expo ’70. As an accomplished educator, Tange taught for most of his career at the University of Tokyo. His architectural laboratory there and the Department of Urban Engineering that he cofounded have trained generations of Japanese architectural and urban thinkers and practitioners. The author would like to thank Professor Yatsuka Hajime in Tokyo and Yihan Yin of University of Pennsylvania for their inputs to this article.
Religious Pluralism
Authors: Harrison Victoria S. 
Published: August 2020

Within the philosophy of religion, theories of religious pluralism are models that provide a philosophical account of religious diversity. They are not descriptive theories of religion, and the terms “religious pluralism” and “religious diversity” are not equivalent in the context of philosophical discussion. Theories of religious pluralism have been present within the philosophy of religion since the 1700s, when G. W. F. Hegel and F. D. E. Schleiermacher established the modern discipline on the understanding that the philosophical study of religion embraced all religions. Religious pluralism came to prominence within the philosophy of religion in the 1980s, with the work of the British philosopher John Hick (b. 1922–d. 2012) being seminal. During the 1990s, philosophical work on religious pluralism and related topics was dominated by the discussion among Hick, his supporters, and his critics. Hick’s theory of religious pluralism is still the most comprehensive and widely discussed in Anglo-American philosophy of religion. In his development of the theory, Hick engaged with and was often influential on work in other areas of philosophy, especially metaphysics, epistemology, and the philosophy of language. This intersection of philosophical concerns continues to make the investigation of religious pluralism a focal point within the philosophy of religion. This article provides references to works that explain the wider methodological context of theories of religious pluralism. It then provides a section covering Hick’s major works on religious pluralism, as well as the most significant responses to his theory. Since the late 20th century, and in the light of the philosophical difficulties attending Hick’s theory, alternative theories of religious pluralism have been proposed. This article provides references to some of the most interesting proposals. The article then hones in on the interface between theories of religious pluralism and epistemology, providing references under these subsections: Religious Diversity and Epistemic Disagreement, Warranted Christian Exclusivism, and Religious Diversity and Religious Experience. Recognizing that some philosophers interested in religious diversity focus on its social, ethical, and political dimensions, this article provides references to the most significant philosophical works related to such practical concerns, insofar as they have a bearing on the discussion of theories of religious pluralism. A section is also provided on Islam and Religious Pluralism, since Muslim philosophers of religion have been especially active in this area. A final section provides references to some key works engaging with religious pluralism from the perspectives of theology and religious studies.
Colonial Place Names
Authors: Stolz Thomas , Warnke Ingo H. , de Bloom Jascha 
Published: August 2020

Colonial place names (= CPNs) constitute a specific category of toponyms, namely the class of place names which are attested in documents of the era of colonialism (c. 1415–c. 1999) as labels employed (a) by (mostly European) colonizers for reference to geo-objects in the territory of the (mostly extra-European) colonized or (b), most frequently in the shape of street-names commemorating events, person, or places related to the colonialist enterprise, as expression of colonial ambitions of (mostly European) colonizers in their home-countries. CPNs are a very promising field of research for students of (not only colonial) history, political science, postcolonialism, law, geography, cartography, literary studies, onomastics, etc. CPNs are crucially involved in the discursive creation of power relations and are relevant to identity issues not the least in the context of decolonization and postcolonial reactions to CPNs. This considerable academic potential notwithstanding, CPNs have only recently been acknowledged as a research objects in their own right. The idea that it is worthwhile studying CPNs comprehensively and systematically has developed within the domain of linguistics, more specifically within the newly established research program of colonial linguistics. Proponents of this innovative branch of language studies have highlighted that across the different (mostly European) colonialisms CPNs display a remarkably homogeneous behavior in the sense that their structural and semantic properties tend to be similar independent of the language of colonizers so that it is possible to postulate a canonical type of CPN. This similarity is a proven fact in the domain of exonyms and hybrids, i.e., in the case of CPNs which consist either completely or partly of elements which are taken directly from the language of the colonizers. As to endonyms (= CPNs which exclusively involve elements which—at least superficially—stem from languages of the colonized), future research will reveal whether it is possible to formulate generalizations also over this segment of the colonial toponomasticons. The study of CPNs calls for interdisciplinary cooperation. Since this cooperation is as yet still in its infancy the bibliography focuses on those scholarly contributions which are equipped with a discernible linguistic component. This means that this article avoids mentioning the extant uncommented gazetteers and other list-like inventories of CPNs as published by colonial or other governmental authorities whose purpose is not of an academic nature.
A workable strategy for COVID-19 testing: stratified periodic testing rather than universal random testing
Authors: Cleevely Matthew , Susskind Daniel , Vines David , Vines Louis , Wills Samuel 
Published: August 2020

Abstract
This paper argues for the regular testing of people in groups that are more likely to be exposed to SARS-CoV-2, to reduce the spread of COVID-19 and resume economic activity. We call this ‘stratified periodic testing’. It is ‘stratified’ as it is based on at-risk groups, and ‘periodic’ as everyone in the group is tested at regular intervals. We argue that this is a better use of scarce testing resources than ‘universal random testing’, as has been recently discussed globally. We find that, under reasonable assumptions and allowing for false negative results 30 per cent of the time, 17 per cent of a subgroup would need to be tested each day to lower the effective reproduction number R from 2.5 to 0.75, under stratified periodic testing. Using the same assumptions the universal random testing rate would need to be 27 per cent (as opposed to 7 per cent as argued by Romer (2020b)). We obtain this rate of testing using a corrected method for calculating the impact of an infectious person on others, and allowing for asymptomatic cases. We also find that the effect of one day’s delay between testing positive and self-isolating is similar to having a test that is 30 per cent less accurate.
Why Do Physicians Choose Pain as a Specialty?
Authors: Belgrade Miles , Belgrade Andrea 
Published: August 2020

Abstract

Objective
Numerous forces shape the practice of pain management: scientific advances, technical advances, societal expectations, public health crises, reimbursement factors, and the parameters of who gets trained and what motivates the trainees. In this observational study, we sought to determine expressed motivations for entering the subspecialty of pain management, and in particular whether applicants were more interested in procedural skills (our hypothesis) or rehabilitative and cognitive practices.

Methods
We analyzed the personal statements of 142 applicants to the University of Minnesota’s pain medicine fellowship program. In addition to those themes, the personal statements were scrutinized for other themes such as interest in teaching and research. Comprehensive vs interventional/procedural interests were coded by a group of four research assistants who were trained using practice essays until they achieved high interrater reliability (alpha &gt; 0.8). Two of the researchers coded for additional themes on a two-point scale indicating presence or absence of a particular theme. When they did not agree, a third researcher broke the tie. Theme prevalence was compared by specialty and gender.

Results
Residents expressed interest in interventional and comprehensive pain practice without significant differences; however, there were specialty and gender differences in other themes such as teaching, research, and leadership in program development.

Conclusions
If pain specialty training is going to meet the needs of prospective residents, patients, and society, we should do more to attract women and neurology and psychiatry residents. We should include more opportunities for research and the flexibility to educate trainees who may not pursue a procedural practice.
Perfectionist Bads
Authors: Bradford Gwen 
Published: August 2020

AbstractPain, failure and false beliefs all make a life worse, or so it is plausible to think. These things and possibly others seem to be intrinsically bad—no matter what further good comes of them they make a life worse pro tanto. In spite of the obvious badness, this is difficult to explain. While there are many accounts of well-being, few are up to the challenge of a univocal explanation of ill-being. Perfectionism has particular difficulty. Otherwise, it is a theory that has quite a lot in its favour. This paper proposes a new valuation scheme for perfectionism, the tripartite scheme, which affords perfectionism the resources to give a comprehensive account of robust bads and has further additional advantages for the view.