bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verification of the analytical performance of a molecular diagnostic for response to anti-PD1 therapy on the nCounter Dx Analysis System.
Authors: Wallden Brett , Pekker Irena , Popa Simina , Dowidar Naeem , Ngouenet Celine , Sullivan Amy , Danaher Patrick , Mashadi-Hossein Afshin , Liu Mingdong , Marton Matthew John , Ferree Sean , Storhoff James Justin 
Published: November 2019

8 Background: Pembrolizumab is a humanized anti-PD1 antibody that is approved for use in advanced melanoma, recurrent or metastatic head and neck squamous cell carcinoma, and metastatic non-small-cell lung cancer. It has also shown clinical activity in a number of other tumor types in clinical trials, but there is need for a precise and accurate test that can identify patients most likely to benefit from therapy. We have previously described the development and analytical performance of a NanoString RNA expression clinical trial assay, referred to here as the Tumor Inflammation Signature (TIS) assay, which is being evaluated as a patient enrichment biomarker in multiple solid tumor types for treatment with pembrolizumab. Here we describe additional performance data and analytical verification of reproducibility from tissue and RNA input range in multiple tumor types. Methods: Linearity and specificity were assessed with single targets or pools of in vitro transcribed RNAs with sequences matching the 18 biomarker and 10 normalization gene probe targets. The verification of the previously reported analytical precision from RNA and reproducibility from tissue was performed using independent samples from 11 tumor types. The biological variability of the signature within a patient sample was evaluated by testing multiple core punches from formalin fixed paraffin embedded (FFPE) tissue blocks. Results: The TIS assay’s measurement of the 28 genes was linear across a wide dynamic range ( ≥ 4 logs) and was highly specific with < 1% cross reactivity between probes. The assay was verified across the specified RNA input range with > 90% concordance at the low end (50ng) of the RNA input range. The total standard deviation of the anti-PD1 Predictor Score from tissue was verified as < 5% of the signature score range and > 90% concordance in biomarker high/low categorization within the biological replicates. Conclusions: The analytical performance of the NanoString TIS assay was verified to be robust. The assay is well suited for decentralized clinical testing and is currently under investigation to identify responders to anti-PD1 therapy in multiple tumor types in several clinical studies.
A 3D image-based quantification of immune cell-tumor spheroid interactions in the presence of checkpoint inhibition.
Authors: Daszkiewicz Lidia , Klop Maarten , Yan Kuan , Price Leo 
Published: November 2019

82 Background: Delivering on the promises of cancer immunotherapy is hampered by a lack of in vitro testing platforms that enable the early selection of promising drugs candidates. While quantification of the number of cytotoxic T cells and IFNγ secretion can give an indication of the drug effect, it is often critical to assess the functional cytotoxicity and infiltration capacity. In addition, immunomodulatory effects of drug combinations need to be carefully assessed before these treatment modalities reach patients. However there are unlimited possibilities of new combinations, especially in the view of synergy effects observed with double checkpoint inhibition blockade and combination with standard of care drugs. To specifically address the needs of immunotherapy cancer drug developers, we developed robust assays that incorporate the human immune system into tumor spheroid cultures, with functional read-outs in a high throughput (384well plate) format. Methods: Breast cancer cells were grown in a hydrogel to form 3D tumoroids. HLA-matched PBMCs with and without pre-activation/exhaustion were added and the infiltration of T cells and subsequent tumoroid killing was quantified. The effect of immune checkpoint blockade was also assessed with the addition of pembrolizumab. Quantification of effects of stimulators and checkpoint inhibition was achieved with 3D imaging and morphometric analysis with OMiner software. Results: Automated 3D image and data analysis enabled discrimination of immune-tumour cell interactions depending on activation status of T cells. Activated T cells more efficiently infiltrated and killed tumoroids than non-activated ones. Cytotoxic activity of overactivated/exhausted T cells was supressed but this could be reversed by the presence of checkpoint inhibitor in the coculture. Conclusions: A 3D environment allows the different cell types to engage in a more realistic setting than when cells are grow in a monolayer. Using image-based analysis, immune-tumor interactions can be dissected. This represents a new, highly powerful tool for cancer immunotherapy drug developers to select the most promising compounds, allowing faster progression towards the clinic.
Immune priming by stereotactic body radiation: Dosimetric characteristics.
Authors: Castaneda Serguei A. , Shah Sunjay A , Huang David , Sims-Mourtada Jennifer , Mourtada Firas 
Published: November 2019

85 Background: A systemic immune response to tumors after stereotactic body radiation therapy (SBRT) has been observed. The role of radiation dosimetry variables in priming an immune response is not well characterized. Methods: We analyzed radiation dosimetry variables in a patient with metastatic melanoma receiving pembrolizumab for about 1 year prior to concurrent use with Cyberknife SBRT for a symptomatic lesion in the right lower lobe of the lung. The patient received 50 Gy in 5 fractions prescribed to the 74% isodose line (using a Monte Carlo dose calculation) and developed a systemic immune response three months after this intervention. Results: We observed priming of the immune system as man ifested by radiological and clinical responses in non-irradiated cervical lymph nodes and a new persistent FDG-avid lesion on PET scan located in the base of the tongue. Given the concern for a new malignancy, the patient underwent hemi tongue base glossectomy; interestingly, this surgical specimen showed tonsillar mucosa with reactive lymphoid hyperplasia without evidence of tumor. Upon review of the CyberKnife SBRT plan, we identified that the planning target volume (PTV) was atypically under covered to 89.9% and also had a relatively high value of gross tumor volume (GTV) conformity index (CI) of 2.1. In our experience with CyberKnife plans for lung lesions, usually the PTV coverage is more than 95% and the GTV CI is less than 1.5. Other dosimetry variables had more typical values, including GTV coverage of 99.9%, PTV CI of 1.1, and both GTV and PTV homogeneity index of 1.4. Conclusions: Relatively low PTV coverage and high GTV CI were associated with immune system priming in a well-documented case of systemic responses in non-irradiated pathological and normal tissues, in the setting of concurrent immunotherapy and SBRT. Further studies are warranted to confirm this association.
Phase II study of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) in Korea.
Authors: Park Keunchil , Cho Eun Kyung , Kang Jin Hyoung , Han Ji-Youn , Lee Jong Seok , Kim Dong-Wan , Kim Sang-We , Cho Byoung Chul , Min Young Joo , Lee Ki Hyeong , Kim Joo-Hang 
Published: November 2019

92 Background: Nivolumab (BMS-936558/ONO-4538), a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in several tumor types. Recently, two phase III studies (CheckMate-017 and -057) demonstrated that nivolumab improved overall survival (OS) than docetaxel in second-line of squamous (SQ) and non-squamous (NSQ) Non-Small Cell Lung Cancer (NSCLC), respectively. Here, we report the results of a phase II study to evaluate the efficacy and safety of nivolumab in Korean patients (pts) with previously treated advanced SQ and NSQ NSCLC. Methods: This study requires pts aged ≥ 20 years with ECOG Performance Status (PS) of 0 or 1, stage IIIB/IV or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen. Pts received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity. The primary endpoint in this study was the objective response rate (ORR) (RECIST v1.1). Results: Nivolumab was administered to 100 NSCLC pts (SQ: 44, NSQ: 56), male/female: 78 (SQ: 44, NSQ: 34)/22 (SQ: 0, NSQ: 22); PS 0/1: 14 (SQ: 6, NSQ: 8)/86 (SQ: 38, NSQ: 48); aged 29 to 80 [median: 66.5] years (SQ: 40 to 80 [median: 69.5], NSQ: 29 to 77 [median: 63.5]); Stage IIIB/IV/recurrence: 6 (SQ: 5, NSQ: 1)/91 (SQ: 37, NSQ: 54)/3 (SQ: 2, NSQ: 1)). In SQ and NSQ NSCLC, ORR was 15.9% (7/44) and 23.2% (13/56), respectively. Median progression-free survival was 2.6 mo and 5.3 mo, respectively. Complete Response was observed in 2.3% (1/44) and 1.8% (1/56), respectively. Median OS was 12.3 mo and 16.3 mo, respectively. Median follow-up was 8.9 mo and 12.3 mo, respectively. Most common adverse drug reaction (ADR) was decreased appetite 15.9% (7/44), followed by pyrexia 9.1% (4/44) in SQ NSCLC, and decreased appetite 12.5% (7/56), followed by pruritus 10.7% (6/56), fatigue 8.9% (5/56), pyrexia 5.4% (3/56) and nausea 5.4% (3/56) in NSQ NSCLC. Grade 3-4 ADR was observed in 6.8% (3/44) and 10.7% (6/56) of SQ and NSQ NSCLC, respectively. No interstitial lung disease and no grade 5 ADRs were observed in this study. Conclusions: Nivolumab was considered to be effective and used safely in Korean pts with SQ and NSQ NSCLC as well as in non-Korean pts with SQ and NSQ NSCLC. Clinical trial information: NCT02175017.
Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.
Authors: Xue Song , Hu Man , Yu Jinming , Fan Bingjie , Ma Ji 
Published: November 2019

94 Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.
Immune checkpoint inhibitor responses in humanized mouse melanoma models using patient-derived xenografts.
Authors: Somasundaram Rajasekharan 
Published: November 2019

99 Background: Melanoma patients develop resistance to both chemo- and targeted-therapy drugs. Promising pre-clinical and clinical results with immune checkpoint inhibitors using antibodies directed against CTLA-4 and PD-1 have re-energized the field of immune-based therapies in melanoma. However, only a third of melanoma patients respond to immune checkpoint blockade. Currently available mouse xenograft and transgenic mouse melanoma models have a number of short comings and are unable to address the basis of drug resistance and immune non-responsiveness that are frequently observed in melanoma patients. Thus there is an urgent need to establish an in vivo model with a human immune microenvironment that can address issues of therapy resistance. Methods: Our laboratory has developed a humanized mouse melanoma model using patient-derived xenografts (PDX). Results: Immunodeficient NSG mice were reconstituted with human CD34+ cells and after 7-9 weeks, mature human CD45+ cells were observed in circulating blood. Humanized mice were then challenged with HLA-matched melanoma PDX and the functional ability of human immune cells to restrict tumor growth was monitored. Delayed tumor growth was observed in humanized mice indicating in vivo sensitization of human immune cells to melanoma. This was confirmed by in vitro demonstration of human lymphocytes from tumor-bearing mice showing enhanced cytokine expression after stimulation with melanoma antigen peptides. Further, cytotoxic T-cells derived from melanoma peptide stimulation were able to functionally lyse tumor cells in vitro. In preliminary therapy studies, a majority of tumor-bearing humanized mice treated with anti-PD-1 antibody showed restricted tumor growth and a combination of BRAF inhibitor and anti-PD1 antibody treatment showed prolonged survival. Conclusions: Our results suggest that humanized mouse melanoma model can be explored further to understand the causes of therapy resistance and immune non-responsiveness.
To Tell or Not to Tell: Exploring the Preferences and Attitudes of Patients and Family Caregivers on Disclosure of a Cancer-Related Diagnosis and Prognosis
Authors: Ghoshal Arunangshu , Salins Naveen , Damani Anuja , Chowdhury Jayeeta , Chitre Arundhati , Muckaden Mary Ann , Deodhar Jayita , Badwe Rajendra 
Published: November 2019

PURPOSE To understand the preferences and attitudes of patients and family caregivers on disclosure of cancer diagnosis and prognosis in an Indian setting. METHODS Overall, 250 adult patients with cancer and 250 family caregivers attending the outpatients of a tertiary cancer hospital for the first time were recruited purposively. The mean ages of patients and caregivers were 49.9 years (range, 23-80 years) and 37.9 years (range, 19-67 years), respectively. Separately, they completed prevalidated, close-ended preference questions and were interviewed for open-ended attitude questions. RESULTS A total of 250 adult patients (response rate, 47.17% overall, 73.2% in men, and 26.8% in women) and 250 family caregivers (response rate, 40.65% overall, 84.0% in men, and 16.0% in women) participated. Significant differences were observed in the preference to full disclosure of the name of illness between patients (81.2%) and caregivers (34.0%) and with the expected length of survival between patients (72.8%) and caregivers (8.8%; P < .001). The patients felt that knowing a diagnosis and prognosis may help them be prepared, plan additional treatment, anticipate complications, and plan for future and family. The caregivers felt that patients knowing a diagnosis and prognosis may negatively affect the future course of illness and cause patients to experience stress, depression, loss of hope, and confidence. CONCLUSION Patients with cancer preferred full disclosure of their diagnoses and prognoses, whereas the family caregivers preferred nondisclosure of the same to their patients. This novel information obtained through a large study with varied participants from different parts of the country will help formulate communication strategies for cancer care.
Encounters in Borderlands
Authors: Bauer Susanne , Güttler Nils , Schlünder Martina 
Published: November 2019

AbstractFocusing on a global hub of aviation, Frankfurt Airport, this essay examines encounters between animals and technology in airport operation. In order to understand how airport practices constantly negotiate the borders with local environments or even produce new ones, we draw on Gloria Anzaldúa’s concept of “borderlands.” Extending this notion from human to nonhuman inhabitants and passengers of airports opens up for novel possibilities to apprehend the affective dimension in the life-technology intersections at airports. In this sense, the airport is a site of multiple borderlands, producing intersections that include material and imaginative, sometimes violent, boundary drawing. We examine a broad set of multispecies borders and “borderlining” practices, their material cultures, and affective economies. What kind of local, historical legacies do airports struggle with and how do they cope with the underlying tensions of partially connected sites, sectors, and spaces? Throughout the essay, we historicize three encounters of the aviation infrastructure and its living environments and their affective economies: borderlining the airfield, borderlining the animal passenger, and borderlining the animal intruder. These examples highlight different modes of encounters, like clashes, coexistence, and care.
Toward an Ethological Poetics
Authors: Cooke Stuart 
Published: November 2019

Abstract
In an attempt to respond to the West’s general obliviousness to nonhuman semiosis, this article proposes a method for appreciating nonhuman poetics. By combining the critical tools of poetics and literary theory with insights from ethology and biosemiotics, Stuart Cooke outlines a method of criticism for nonhuman creative compositions. Drawing on the work of Gerald Bruns, Elizabeth Grosz, and Gilles Deleuze and Félix Guattari, Cooke begins by theorizing a poetics that attends to the ecology of forces that produce, and are produced by, a work rather than the intentions of a single artist. Cooke proposes that an ethological poetics emphasizes the expressive capacity of materials across a range of written, musical, visual, and performative structures. By studying these expressive forces, Cooke argues, we can extend our appreciation of art and poetics into multispecies domains. The challenge is not to focus on the “meaning” or intention of nonhuman artworks but to study their disruptive, and exciting, forces. The third part of the essay is a case study of an Australian songbird, the Albert’s lyrebird, whose remarkable performance Cooke reads in terms of an ethological poetics. Producing an operatic complex of song, instrumentation, dance, and stage design, the male lyrebird’s composition is thoroughly entangled with the flora and fauna of his umwelt. Resistant to categorization by any generic label, Cooke argues that the lyrebird’s composition is best approached in the terms of transgressive, avant-garde performative and sound poetics—although it escapes such terms, thinking about the bird’s composition in this way compels us into a relation with its territory.
Death of a Guinea Pig
Authors: García María Elena 
Published: November 2019

AbstractDuring ethnographic research on the biopolitics of culinary nationalism in Peru, I visited a guinea pig breeding farm north of Lima. Guinea pigs are considered “food animals” in the Andes. That encounter with pregnant guinea pigs—and with one guinea pig in particular who was tossed out of her enclosure and left to die—led me to a visceral questioning of my methodological and political approaches to and commitments in multispecies ethnography. I found myself uncomfortably close to the deaths of these female bodies yet unable to voice my dismay or grief. This essay is a modest effort to theorize what grief has to offer the practice of multispecies ethnography. I explore how writing about the ethnographic encounter as one of tragedy and loss might open up the productive possibilities of mourning and grief in connecting human and nonhuman worlds.
Remixing Transfeminist Futures
Authors: Samer Rox 
Published: November 2019

Abstract
There are likely many ways to remix transfeminist futures. As a scholar-vidder, I focus on vidding as one form this work might take. Vidding is an especially affective form of remix art that renders literal the Foucauldian imperative “knowledge is not made for understanding; it is made for cutting.” In disturbing what was previously considered immobile, fragmenting what was thought unified, and not hiding the cuts with which it does so, vidding produces affective surplus. It is not only that a vid disassembles source media, but that its reassembly produces more than a new text; it also, often unpredictably and inexplicably, generates entirely new affects. Taken up as a transfeminist creative critical praxis, vidding could challenge the transphobic and cissexist common sense on which our reality relies, including its teleological histories that cast trans as “new,” ignoring the contributions of trans people to feminist and queer movements and the historical and geographical range of gender variance; liberal discourses that approach trans as yet another matter of civil rights, neglecting how visibility renders trans people more susceptible to violence and surveillance; and media narratives which tell the same fetishizing, isolating, and tragic stories of trans lives time and again. Through my analysis of three of my own transfeminist vids, I introduce the digital humanities methodology “remixing transfeminist futures” and propose we remix our transphobic, transmisogynistic, cissexist reality so as to make perceptible a future when trans people, queer people, people of color, and all women and femmes are free.
Treatment and Prognosis of Radiation-Associated Breast Angiosarcoma in a Nationwide Population
Authors: Salminen Samuli H. , Wiklund Tom , Sampo Mika M. , Tarkkanen Maija , Pulliainen Lea , Böhling Tom O. , Tukiainen Erkki , Hukkinen Katja , Blomqvist Carl P. 
Published: November 2019

AbstractBackgroundRadiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment.MethodsA search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival.ResultsOverall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4–15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival.ConclusionsWe found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good.