scholarly journals Anti-PD-1 checkpoint blockade monotherapy in the orthotopic GL261 glioma model: the devil is in the detail

2021 ◽  
Author(s):  
Zachariah P Tritz ◽  
Katayoun Ayasoufi ◽  
Aaron J Johnson
Keyword(s):  
Tumor Location ◽  
Checkpoint Blockade ◽  
Clinical Model ◽  
Fine Grained ◽  
Biological Variables ◽  
Gl261 Cell ◽  
The Devil ◽  
Treatment Responsiveness ◽  
Chemotherapeutic Interventions ◽  
Made In

Abstract The GL261 cell line, syngeneic on the C57BL/6 background, has, since its establishment half a century ago in 1970, become the most commonly used immunocompetent murine model of glioblastoma. As immunotherapy has entered the mainstream of clinical discourse in the past decade, this model has proved its worth as a formidable opponent against various immunotherapeutic combinations. Although advances in surgical, radiological, and chemotherapeutic interventions have extended mean glioblastoma patient survival by several months, five year survival post-diagnosis remains under 5%. Immunotherapeutic interventions, such as the ones explored in the murine GL261 model, may prove beneficial for patients with glioblastoma. However, even common immunotherapeutic interventions in the GL261 model still have unclear efficacy, with wildly discrepant conclusions being made in the literature regarding this topic. Here, we focus on anti-PD-1 checkpoint blockade monotherapy as an example of this pattern. We contend that a fine-grained analysis of how biological variables (age, sex, tumor location, etc…) predict treatment responsiveness in this pre-clinical model will better enable researchers to identify glioblastoma patients most likely to benefit from checkpoint blockade immunotherapy moving forward.

Association of the diversity and composition of the gut microbiome with responses and survival (PFS) in metastatic melanoma (MM) patients (pts) on anti-PD-1 therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3008-3008 ◽  
Author(s):  
Jennifer Ann Wargo ◽  
Vancheswaran Gopalakrishnan ◽  
Christine Spencer ◽  
Tatiana Karpinets ◽  
Alexandre Reuben ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Large Cohort ◽  
Checkpoint Blockade ◽  
Cancer Types ◽  
Pre Treatment ◽  
Immune Profiling ◽  
Made In

3008 Background: Significant advances have been made in cancer therapy with immune checkpoint blockade. However, responses in pts with MM are variable, and insights are needed to identify biomarkers of response and strategies to overcome resistance. There is a growing appreciation of the role of the microbiome in cancer, and evidence in murine models that modulation of the gut microbiome may enhance responses to immune checkpoint blockade, though this has not been well studied in pts. Thus we evaluated the microbiome in a large cohort of pts with MM, focusing on responses to anti-PD-1. Methods: We collected oral (n = 234) and gut microbiome samples (n = 120) on a large cohort of of MM patients (n = 221). Of note, the majority of pts were treated with PD-1 based therapy (n = 105). Pts on anti-PD1 were classified as either responders (R) or non-responders (NR) based on RECIST criteria, and 16S rRNA and whole genome shotgun (WGS) sequencing were performed. Immune profiling (via immunohistochemistry, flow cytometry, cytokines and gene expression profiling) was also done in available pre-treatment tumors at baseline. Results: Significant differences in diversity and composition of the gut microbiome were noted in R vs NR to anti-PD-1, with a higher diversity of bacteria in R vs NR (p = 0.03). Differences were also noted in the composition of gut bacteria, with a higher abundance of Clostridiales in R and of Bacteroidales in NR. Immune profiling demonstrated increased tumor immune infiltrates in R pts , with a higher density of CD8+T cells; this correlated with abundance of specific bacteria enriched in the gut microbiome (r = 0.59, 0.014). Other features of enhanced immunity were also noted, and WGS revealed differential metabolic signatures in R vs NR. Furthermore, diversity (p = 0.009; HR = 7.67) and abundance of specific bacteria in R (p = 0.007; HR = 3.88) was associated with improved PFS to anti-PD-1 therapy. Conclusions: Diversity and composition of the gut microbiome differ in R vs NR pts with MM receiving anti-PD-1 therapy. These have potentially far-reaching implications, though results need to be validated in larger cohorts across cancer types.

scholarly journals Reform of the Mental Health Act 1983 – Convention Implications of the Green Paper

2014 ◽  
pp. 99
Author(s):  
Paul Bowen
Keyword(s):  
Mental Health ◽  
Human Rights ◽  
Green Paper ◽  
Mental Health Act ◽  
Human Rights Act ◽  
Human Rights Act 1998 ◽  
The Government ◽  
The Impact ◽  
The Devil ◽  
Made In

Assessing the Convention compatibility of the Government proposals for reform of the Mental Health Act 1983 set out in the Green Paper1 is largely an exercise in speculation, for three reasons.First, the proposals are very broad; the detail, where the devil may be found, is yet to come.Second, the Convention does not permit the Strasbourg authorities to review the legality of national legislation in the abstract, but only with reference to particular cases after the proceedings are complete2. Although that will not necessarily preclude a domestic court from reviewing the lawfulness of any provision of the new Mental Health Act after incorporation of the Human Rights Act 19983, the comments that can be made in this article are necessarily confined to the<br />general rather than the specific.Third, and perhaps most significantly, it is impossible to predict the impact of the Convention following the coming into force of the Human Rights Act 1998 on 2 October 2000.

scholarly journals Hydraulic Conductivity of Quarry Dust with Sandy Soils

2019 ◽  
Vol 8 (12S) ◽  
pp. 1030-1033
Keyword(s):  
Hydraulic Conductivity ◽  
Sandy Soils ◽  
Research Center ◽  
Fine Grained ◽  
Covering Material ◽  
Previous Decade ◽  
The Impact ◽  
Quarry Dust ◽  
Made In ◽  
Pressure Driven

Water driven conductivity of soil is a significant property in Geotechnical Engineering, because of the way that a large number of the issues related with the plan and development of structures require the assurance of porousness of the dirt ( e.g., dewatering of unearthed locales, leakage through dams, and so forth.). Additionally the requirement for the assessment of the water driven conductivity of fine grained soils utilized as covering material for the regulation of squanders has created a lot of enthusiasm during the previous decade. An endeavor is made in this paper to ponder the impact of compaction on water powered conductivity of sandy soils through consistent head penetrability test in the research center. In this examination the impacts of three degrees of compaction on the water powered properties of two sandy soils and one quarry dust is assessed. Pressure driven conductivities are essentially diminished by the most noteworthy compaction level for every one of the examples. The outcomes show that dirt compaction could unequivocally impact, in various ways, the pressure driven properties of the dirts.

scholarly journals Automatic Table Detection, Structure Recognition and Data Extraction from Document Images

2021 ◽  
Vol 10 (9) ◽  
pp. 73-79
Author(s):  
Borra Vineetha ◽  
◽  
D. N. D. Harini ◽  
Ravi Yelesvarupu ◽  
◽  
...  
Keyword(s):  
Internal Structure ◽  
Data Extraction ◽  
Electronic Devices ◽  
Tabular Form ◽  
Document Images ◽  
Fine Grained ◽  
Structure Recognition ◽  
Recent Advancement ◽  
Table Data ◽  
Made In

In the recent advancement, the extensive usage of electronic devices to photograph and upload documents, the requirement for extracting the information present in the unstructured document images is becoming progressively intense. The major obstacle to the objective is, these images often contain information in tabular form and extracting the data from table images presents a series of challenges due to the various layouts and encodings of the tables. It includes the accurate detection of the table present in an image and eventually recognizing the internal structure of the table and extracting the information from it. Although some progress has been made in table detection, obtaining the table contents is still a challenge since this involves more fine-grained table structure (rows and columns) recognition. The digitization of critical information has to be carried out automatically since there are millions of documents. Based on the motivation that AI-based solutions are automating many processors, this work comprises three different stages: First, the table detection using Faster R-CNN algorithm. Second, table internal structure recognition process using morphology operation and refine operation and last the table data extraction using contours algorithm. The dataset used in this work was taken from the UNLV dataset.

Locally advanced or metastatic pancreatic adenocarcinoma (PA): Prognostic factors for prolonged survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15134-e15134
Author(s):  
Anne Ploquin ◽  
Camille Cozzolino ◽  
Stephanie Truant ◽  
Guillaume Piessen ◽  
Christophe Desauw ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Pancreatic Head ◽  
Median Number ◽  
Tumor Location ◽  
Male Gender ◽  
Prolonged Survival ◽  
Predictive Values ◽  
Biological Variables

e15134 Background: Prognosis of pts with locally advanced or metastatic PA is poor, with median survival of 6-9 months. Yet, since the use of gemcitabine, some patients survive more than one year. Recently, FOLFIRINOX regimen yielded better results in selected patients, but with more toxicity. We assessed the value of baseline predictive factors of prolonged survival in non-selected pts treated with gemcitabine. Methods: We conducted a monocentric, retrospective study (1999 to 2010) on all pts treated for locally advanced or metastatic PA. Demographical, clinical, tumoral and biological variables were included into the analysis. The primary end-point was the 12 months survival. All parameters were assessed in univariate and multivariated analyses. We then built a prognostic scoring system integrating the independent prognostic factors. Results: The study was performed on 160 pts: median age 61.1 years, sex ratio (M/F) 93/67, ECOG 0-1/2-3: 60/98, jaundice 62 (38.8%), initially resectable : 36 (22.5%), intra-pancreatic primary location: head: 110 (68.8%), body: 19 (11.9%), tail: 27 (16.9%). The adenocarcinoma was histologically document in 124 cases (77.5%). The median number of metastasis sites was 1 (71.3% liver). The median Ca 19-9 concentration was 925 IU/ml. 155 pts (96.9%) received chemotherapy, of which 124 (80.0%) with gemcitabine in first line. Fifty-two patients (32.5%) were alive 12 months after diagnosis. In univariate analysis, male gender, PS, initial stage, differentiation, primary tumor location, Ca 19-9 were prognostic factors. In multivariate analysis, male gender, head or body locations and low Ca 19-9 concentration (< 111 IU/ml) were associated with a better prognosis. The score with a cut-off between 2 and 3 points was discriminant, with positive and negative predictive values of 64.7% IC-95% [59.2-70.2] and 75.3% IC-95% [74.4-76.2], respectively. The rate of correctly classified pts was 73.6% IC-95% [72.8-74.4]. Conclusions: Male gender, pancreatic head or body location, and Ca 19-9 < 111 are independent prognostic factors for prolonged survival. Further analyses are needed to determine more accurately pts suitable for gemcitabine or the more recently validated regimen FOLFIRINOX.

scholarly journals Morphological Analysis of the Glorious Qur'an: A Comparative Survey of Three Corpora

2017 ◽  
Author(s):  
Arab World English Journal ◽  
Yasser Muhammad Naguib Sabtan
Keyword(s):  
Morphological Analysis ◽  
Academic Community ◽  
Fine Grained ◽  
Pos Tagging ◽  
Part Of Speech ◽  
Comparative Survey ◽  
The University ◽  
Manual Verification ◽  
Made In

Some attempts have been made in the academic community to carry out an automatic morphological analysis of the Qur'anic text. Among the well-known endeavors in this regard is the morphological annotation of the Quranic Arabic Corpus (QAC) which was carried out in Leeds University, UK. In addition, researchers in the University of Haifa had previously implemented a computational system for the morphological analysis of the Qur'an. More recently, a new Quranic corpus has been built in Mohammed I University in Morocco. To the best of our knowledge, these are the only three studies to produce a morphologically analyzed part-of-speech tagged Qur'an encoded as a structured linguistic database. This paper surveys the morphological analysis in the above-mentioned annotation projects and compares between them to test the quality of their analysis using five criteria related to display of the text in the corpus, word segmentation, morphological disambiguation, part of speech (POS) tag set and manual verification. The paper concludes that the QAC of Leeds and the Quranic corpus of Morocco surpass the Quranic corpus of Haifa with regard to most of these criteria. Furthermore, some additional POS tags for derivative nouns are suggested in a step to reach a more fine-grained tag set that could be proposed for POS tagging of Qur'anic Arabic.

Understanding context in computer-mediated communication

2021 ◽  
Author(s):  
Jennifer Yameng Liang
Keyword(s):  
Computer Mediated Communication ◽  
Mainland China ◽  
Online Video ◽  
Mediated Communication ◽  
Fine Grained ◽  
Computer Mediated ◽  
Media Platform ◽  
Context Of Situation ◽  
Computer Mediated Communications ◽  
Made In

Abstract With unprecedented transformations taking place in the landscape of what to say and how we mean, interactions in the digital age take on various new forms of doing and being. To make sense of “what it is that is going on” requires an understanding of the context wherein the computer-mediated communications take place. Focusing on a burgeoning online video commenting discourse in mainland China called Danmaku (a media feature that projects viewer comments in the form of “bullet chains” overlaid on the video), the present study applies the schematic construct of context of situation and its paradigmatic representations developed in Systemic Functional Linguistics to a functionally-driven discussion of Danmaku context. Drawing on a corpus of comments from 18 well-received videos on Bilibili.com (a major Danmaku site in mainland China), the study provides a fine-grained analysis that highlights emergent technological and semiotic variables in the Danmaku Mode, such as anonymity, invisibility, dynamicity, and pseudo-synchronicity. It then discusses how these variables mediate the properties of Field and Tenor and further impinge upon the experiential and interpersonal meanings made in Danmaku communication. The analysis has also highlighted the carnivalesque nature of Danmaku which makes it an increasingly popular social media platform in mainland China.

scholarly journals The Devil is in the Channels: Mutual-Channel Loss for Fine-Grained Image Classification

2020 ◽  
Vol 29 ◽  
pp. 4683-4695 ◽  
Author(s):  
Dongliang Chang ◽  
Yifeng Ding ◽  
Jiyang Xie ◽  
Ayan Kumar Bhunia ◽  
Xiaoxu Li ◽  
...  
Keyword(s):  
Image Classification ◽  
Fine Grained ◽  
Channel Loss ◽  
The Devil
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