bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant pheochromocytoma: A comprehensive genomic profiling study.
Authors: Bratslavsky Gennady , Necchi Andrea , Shapiro Oleg , Jacob Joseph , Gay Laurie M. , Alexander Brian Michael , Elvin Julia Andrea , Vergilio Jo-Anne , Killian Jonathan Keith , Nho Nhu Thi , Ramkissoon Shakti , Severson Eric Allan , Hemmerich Amanda , Ali Siraj Mahamed , Chung Jon , Reddy Venkataprasanth P. , Miller Vincent A. , Schrock Alexa Betzig , Liu Nick , Ross Jeffrey S. 
Published: March 2019

508 Background: Malignant pheochromocytomas (MP) are a rare form of endocrine malignancy which can occur in familial and sporadic clinical settings. We performed comprehensive genomic profiling (CGP) to characterize the genomic alterations (GA) in MP and to enable the search for potential therapy targets. Methods: From a series of 181,782 consecutive clinical cases, 43 cases of clinically advanced MP underwent CGP using a hybrid-capture based commercial assay to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. IHC for PD-L1 expression was performed on a subset of patients (DAKO 22C3 antibody). Results: All patients had clinically advanced recurrent and/or metastatic disease. There were 33 (77%) of MP known to have originated in the adrenal gland and 10 (23%) of the MP were sequenced from metastatic site. The primary tumor was used for sequencing in 13 (30%) of the MP cases and a non-primary tumor metastatic site (liver, lung, bone, soft tissue, lymph node, kidney, peritoneal cavity, and chest wall) in 30 (70%) of the MP cases. There were 2.3 GA/tumor. The most frequent un-targetable GA were ATRX (26%), TP53 (21%), SDHB (11%), CTNNB1 (7%), VHL (7%), and CDKN2A/2B, PIK3R2, NOTCH2 and MEN1 (all 5%). The most frequent potentially targetable GA included RET (9%), NF1 (9%) and FGFR1 (5%). PBRM1 GA were found in 2% of MAP. Germline mutations in known cancer predisposition genes were predicted in 7 (16%) of cases involving SDHB (4 cases) and BRCA1, MEN1, and MSH2 (1 case each). The mean TMB was 2.95 mutations/Mb, the median TMB was 2.4 mutations/Mb. 0 (0%) of 33 MP evaluated for MSI had a MSI-High status. Conclusions: MP represent a rare form of endocrine cancer that feature a variety of genomic alterations. Although the GA/tumor is relatively low for MP, CGP can reveal important potential targets for therapy in the metastatic setting including RET, NF1 and FGFR1. MAP do not reveal strong potential for immunotherapy with low TMB, absence of MSI-High status and low (2%) PBRM1 mutation frequencies. Based on this data, further study of CGP as a method of developing precision therapies for MP appears warranted.
Predicting vital retroperitoneal residual tumors of metastatic testicular tumor patients after chemotherapy using radiomics.
Authors: Nestler Tim , Baeßler Bettina , Pinto dos Santos Daniel , Pfister David J. K. P. , Maintz David , Heidenreich Axel 
Published: March 2019

527 Background: About 50% of patients undergoing post-chemotherapy retroperitoneal lymph node dissection (pcRPLND) are overtreated due to missing markers or valid prediction scores prior surgery. The potential of radiomics and machine learning applied on computed tomography (CT) imaging to predict the presence of viable tumor or teratoma in retroperitoneal lymph node metastases from germ cell tumor (GCT) patients prior to pcRPLND has not been explored. Therefore, we applied radiomics and machine learning to CT images of GCT patients prior to pcRPLND. Methods: Metastasized GCT patients who were treated with chemotherapy and received a contrast-enhanced CT prior to pcRPLND possessing complete clinical data were included in the study. Only lymph nodes which were identified in the CT images and correlated with the pathological findings (benign: necrosis / fibrosis vs. viable: viable tumor/ teratoma) were included. Lymph nodes identified in the CT images, were semiautomatically segmented and 93 radiographic features were analyzed. A linear support vector machine (SVM) algorithm was applied to analyze reproducible radiomics features. Additionally, a continuous reduction of the features analyzed was performed using Random Forest algorithms, as well as consecutive correlation and receiver operating curve analyzes. Results: Forty-two patients fulfilled the inclusion criteria and were included in the study. Total in these patients 96 lymph nodes were segmented on CT. Histologically, 41 lymph nodes were classified as viable tumors and 55 as benign. To train the SVM, 67 lymph nodes were randomly selected. Of the 93 radiomic features analyzed, 51 features were reproducible. Applying the trained algorithm to the remaining 29 lymph nodes resulted in a classification accuracy of 82% with a diagnostic sensitivity of 81% and a specificity of 83%. After multistep feature reduction, the three most important predictors for viable tumor achieved a sensitivity of 66% and a specificity of 78% when combined in a multivariate model. Conclusions: The applied radiomics model, solely based on CT images achieved a good sensitivity and specificity in predicting viable metastases.
Efficacy and safety of nivolumab in patients with non-clear cell renal cell carcinoma (RCC): Results from the phase IIIb/IV CheckMate 374 study.
Authors: Vogelzang Nicholas J. , McFarlane Joshua Jemison , Kochenderfer Mark D. , Molina Ana M. , Arrowsmith Edward , Bauer Todd Michael , Hauke Ralph J. , Jain Rohit , Somer Bradley G. , Lam Elaine Tat , Doshi Gurjyot K. , Gunuganti Vijay , Zhang Joshua , Zhao Huanyu , Johansen Jennifer , Tykodi Scott S. 
Published: March 2019

562 Background: Initial safety results from the phase 3b/4 CheckMate 374 study showed that flat-dose nivolumab (NIVO) at 240 mg every 2 wk (Q2W) had a consistent safety profile across patients (pts) with clear cell and non-clear cell advanced RCC. We report updated safety and first disclosure of efficacy for pts with non-clear cell RCC (nccRCC) in CheckMate 374. Methods: Eligible pts in this cohort were adults with advanced or metastatic nccRCC who received 0–3 prior systemic therapies. Pts received NIVO 240 mg IV Q2W for ≤24 mo or until confirmed progression, unacceptable toxicity, or withdrawal of consent. Pts who benefited after 24 mo continued treatment according to the standard of care. The primary endpoint was incidence of high-grade immune-mediated adverse events (IMAEs). Exploratory endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: In CheckMate 374, 44 pts had nccRCC. Histological subtypes included papillary (n = 24), chromophobe (n = 7), unclassified (n = 8), and other (n = 5). Most pts with nccRCC (66%) were treatment-naïve. After a median follow-up of 11.1 mo, median OS was 16.3 mo (95% confidence interval [CI] 9.2–not estimable [NE]). OS was similar regardless of baseline PD-L1 expression. ORR was 13.6% (95% CI 5.2–27.4). One pt had complete response (chromophobe histology) and 5 pts had partial response (2 pts with papillary and 1 pt each with chromophobe, collecting duct, and unclassified histology). Median DOR was 10.2 mo (95% CI 5.6–NE). Median PFS was 2.2 mo (95% CI 1.8–5.4). The 1-year PFS rate was 14% (95% CI 5–27). No new safety concerns were identified. No treatment-related grade 5 AEs or grade 3–4 IMAEs were reported. Conclusions: Clinically meaningful antitumor activity was observed in the first prospective study of NIVO monotherapy in nccRCC. Responses were observed in several histological subtypes. The safety profile of flat-dose NIVO at 240 IV Q2W is consistent with the initial outcomes reported from this study and across the NIVO program. Clinical trial information: NCT02596035.
The association of anxiety and depression with mortality risk among patients with clear cell renal cell carcinoma undergoing nephrectomy.
Authors: Packiam Vignesh T. , Tsivian Matvey , Tyson Mark D. , Lohse Christine M. , Cheville John C. , Boorjian Stephen A. , Leibovich Bradley C. , Thompson Robert Houston 
Published: March 2019

617 Background: Anxiety and depression are psychosocial factors which have been demonstrated to have mixed interactions with mortality across various malignancies. While these variables have been associated with poor overall survival for patients with metastatic RCC, the influence on outcomes for localized RCC has been poorly studied. We evaluated the association of anxiety or depression with survival in patients with surgically treated localized clear cell RCC (ccRCC). Methods: We performed retrospective review of our institutional nephrectomy registry to identify 1,990 patients who underwent radical or partial nephrectomy for unilateral, sporadic, non-metastatic ccRCC between 1995- 2011. Baseline anxiety and depression were identified using ICD-9 codes. Associations of anxiety or depression with outcomes of interest were evaluated using Cox proportional hazards models. Two propensity score (PS) techniques were used: adjusting for PS quintile and re-weighting by stabilized inverse probability weights. Results: A total of 197 (10%) patients had diagnoses of anxiety or depression (57 had anxiety alone, 107 had depression alone, and 33 had both anxiety and depression). Median follow-up among survivors was 10.0 (IQR 7.3-13.6) years, during which time 864 died, including 363 from RCC. Patients with anxiety or depression were younger (mean age 59 vs 62 years, p < 0.001) and had more recent operations (75% vs 47% in 2005-2011, p < 0.001) compared to those with neither diagnosis. After PS adjustment, all clinical and pathologic features were well balanced between groups. After PS adjustment, there were no significant differences in time to local ipsilateral recurrence, distant metastases, and death from RCC between groups. We did note a trend to poorer overall survival in patients with anxiety or depression (HR 1.29, 95%CI = 0.98-1.69, p = 0.065). Conclusions: Our results suggest that neither anxiety nor depression is significantly associated with oncologic outcomes among patients with localized surgically treated ccRCC. The trend toward worse overall survival among patients with anxiety or depression warrants further investigation.
Phase I/II dose-escalation trial of fractionated dose 177Lu-J591 plus 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tagawa Scott T. , Niaz Muhammad Junaid , Osborne Joseph , Vallabhajosula Shankar , Beltran Himisha , Harshman Lauren Christine , Nanus David M. , Molina Ana M. , Faltas Bishoy Morris , Hackett Amy , Gracey Lauren , Sreekumar Jyothi , Babich John , Ballman Karla V. , Bander Neil Harrison 
Published: March 2019

TPS339 Background: PC is a radiosensitive disease. PSMA is selectively overexpressed in advanced PC with upregulation by androgen receptor (AR) pathway dysregulation; limited expression exists in other organs. Prior studies of beta-emitting radiolabeled anti-PSMA antibody J591 demonstrated accurate targeting, efficacy with dose-response effect, and safety with predictable dose-limiting myelosuppression. Recent prospective trials have shown efficacy and safety of 177Lu-PSMA-617 in mCRPC. Studies demonstrate different binding sites of J591 and PSMA-617 and co-administration leads to non-competitive additive binding and delivery of payloads to PSMA+ cells. As the pharmacokinetics and biodistribution of the 2 agents is mostly non-overlapping (other than tumor) and given our prior dose-response data, we hypothesize that delivery of the combination will yield higher tumor delivery with less off-target toxicity (i.e. better responses without increased toxicity). Methods: Men with progressive mCRPC following at least 1 potent AR-targeted agent (e.g. abi/enza) and docetaxel (or unfit/refuse chemo) with metastatic disease on CT/MRI or bone scan without limit of # prior therapies (excluding bone-targeted beta-emitting radioisotopes) provided adequate organ function will be enrolled. Pre-treatment 88Ga-PSMA-11 will be performed, but results are not used for eligibility. Treatment includes fractionated 177Lu-J591 at a fixed moderate dose with escalating doses of 177Lu-PSMA-617 (7.4 – 18.5 GBq per cycle, fractionated D1 and D15) in a 3+3 dose-escalation study. Dose-limiting toxicity (DLT) is defined as attributable grade > 3 heme toxicity or grade > 2 non-heme toxicity. Following determination of recommended phase 2 dose (RP2D), the phase 2 portion will enroll in a 2-stage design. Primary endpoints: DLT and RP2D (ph 1) and PSA decline proportion (ph 2). Secondary endpoints include toxicity, radiographic response, PFS, rPFS, OS, CTC count changes. Correlatives include baseline/follow up PSMA imaging, whole body distribution of 177Lu, tissue and circulating genomic assessment, immunologic assessment, and patient reported outcomes (FACT-P and BPI-SF). Clinical trial information: NCT03545165.
The Politics of Fiction
Authors: Rancière Jacques 
Published: March 2019

Abstract
This essay uses constructions of avowed fiction from modern Western literature and criticism (Erich Auerbach, Virginia Woolf, William Faulkner) to question the sense of reality constructed by dominant social discourses that claim to be the mere expression of reality. Avowed fiction has in fact an “epistemological” privilege: it is not obliged to deny its fictional character. It must build and make visible these modes of presentation of situations and the connection of events that appear elsewhere to be imposed by the very obviousness of the real. In such a way it can better teach us the multiple ways of creating a sense of reality and their links with the forms of the social order.
The X of Representation
Authors: Marriott David 
Published: March 2019

Abstract
This essay is a study of the notion of representation—its relation to difference, politics, diaspora, otherness, truth, and doxa—within Stuart Hall’s work. The reevaluation of this concept in terms of dialectics and différance, or of blackness and innocence, is shown to be an abiding preoccupation of Hall’s work. In particular, because blackness (or its notion) is never innocent, this essay explores the consequences of a certain undecidability that attends any encounter between representation and difference. And it is this X—its shaping of black meaning and life—that alerts us to an unsettling tension in Hall’s work that no knowledge or encounter can fill and that leads to a purely negative reassessment of the racial imperatives of certain truths.
Cardiac phenotype in mouse models of systemic autoimmunity
Authors: Sanghera Chandan , Wong Lok Man , Panahi Mona , Sintou Amalia , Hasham Muneer , Sattler Susanne 
Published: March 2019

ABSTRACT
Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.
The development and evaluation of an online application to assist in the extraction of data from graphs for use in systematic reviews
Authors: Cramond Fala , O'Mara-Eves Alison , Doran-Constant Lee , Rice Andrew SC , Macleod Malcolm , Thomas James 
Published: March 2019

Background:The extraction of data from the reports of primary studies, on which the results of systematic reviews depend, needs to be carried out accurately. To aid reliability, it is recommended that two researchers carry out data extraction independently. The extraction of statistical data from graphs in PDF files is particularly challenging, as the process is usually completely manual, and reviewers need sometimes to revert to holding a ruler against the page to read off values: an inherently time-consuming and error-prone process.Methods:To mitigate some of the above problems we integrated and customised two existing JavaScript libraries to create a new web-based graphical data extraction tool to assist reviewers in extracting data from graphs. This tool aims to facilitate more accurate and timely data extraction through a user interface which can be used to extract data through mouse clicks. We carried out a non-inferiority evaluation to examine its performance in comparison with participants’ standard practice for extracting data from graphs in PDF documents.Results:We found that the customised graphical data extraction tool is not inferior to users’ (N=10) prior standard practice. Our study was not designed to show superiority, but suggests that, on average, participants saved around 6 minutes per graph using the new tool, accompanied by a substantial increase in accuracy.Conclusions:Our study suggests that the incorporation of this type of tool in online systematic review software would be beneficial in facilitating the production of accurate and timely evidence synthesis to improve decision-making.
Developing and implementing an interventional bundle to reduce mortality from gastroschisis in low-resource settings
Authors: Wright Naomi , Abantanga Francis , Amoah Michael , Appeadu-Mensah William , Bokhary Zaitun , Bvulani Bruce , Davies Justine , Miti Sam , Nandi Bip , Nimako Boateng , Poenaru Dan , Tabiri Stephen , Yifieyeh Abiboye , Ade-Ajayi Niyi , Sevdalis Nick , Leather Andy 
Published: March 2019

Background: Gastroschisis is associated with less than 4% mortality in high-income countries and over 90% mortality in many tertiary paediatric surgery centres across sub-Saharan Africa (SSA). The aim of this trial is to develop, implement and prospectively evaluate an interventional bundle to reduce mortality from gastroschisis in seven tertiary paediatric surgery centres across SSA. Methods: A hybrid type-2 effectiveness-implementation, pre-post study design will be utilised. Using current literature an evidence-based, low-technology interventional bundle has been developed. A systematic review, qualitative study and Delphi process will provide further evidence to optimise the interventional bundle and implementation strategy. The interventional bundle has core components, which will remain consistent across all sites, and adaptable components, which will be determined through in-country co-development meetings. Pre- and post-intervention data will be collected on clinical, service delivery and implementation outcomes for 2-years at each site. The primary clinical outcome will be all-cause, in-hospital mortality. Secondary outcomes include the occurrence of a major complication, length of hospital stay and time to full enteral feeds. Service delivery outcomes include time to hospital and primary intervention, and adherence to the pre-hospital and in-hospital protocols. Implementation outcomes are acceptability, adoption, appropriateness, feasibility, fidelity, coverage, cost and sustainability. Pre- and post-intervention clinical outcomes will be compared using Chi-squared analysis, unpaired t-test and/or Mann-Whitney U test. Time-series analysis will be undertaken using Statistical Process Control to identify significant trends and shifts in outcome overtime. Multivariate logistic regression analysis will be used to identify clinical and implementation factors affecting outcome with adjustment for confounders. Outcome: This will be the first multi-centre interventional study to our knowledge aimed at reducing mortality from gastroschisis in low-resource settings. If successful, detailed evaluation of both the clinical and implementation components of the study will allow sustainability in the study sites and further scale-up. Registration: ClinicalTrials.gov Identifier NCT03724214.
KLITIK –NYA DALAM BAHASA INDONESIA
Authors: Pastika I Wayan 
Published: March 2019

The –nya clitic is discussable in terms of not only microlinguisctic domains (phonology, morphology and syntax) but also macrolinguistic perspectives like pragmatics and sociolinguistics. In terms of microlinguistics, there are three important findings of the –nya clitic structure : it can appear (a) as a genitive form, (b) as a definite marker, and (c) as a third person pronoun attached to different word categories (verbs, adjectives, and adverbs). Pragmatically speaking, the –nya clitic can distinguish ‘the old information’ from ‘the new one’ overtly and covertly. From the sociolinguistic point of view the –nya clitic is functioned to avoid the use of the second person that directly threatens the interlocutor’s face. The –nya clitic is also used to measure the degree of closeness between the addresser and the addressee (speech participants): the use of -nya indicates closer relationship (as in bukunya mana?), whereas the use of second person forms indicates formality (as in Dimana Buku Anda?). In informal situations, the speaker tends to choose the third person–nya as a marked form instead of the second person forms such as Anda, kamu, Saudara, Bapak, Ibu, and Dik, which are unmarked. Therefore, the –nya clitic is grammatically, pragmatically, and sociolinguistically very dynamic in different speech registers.
KARAKTERISTIK BAHASA INDONESIA ORANG MINANGKABAU
Authors: Almos Rona , Reniwati Reniwati , Noviatri Noviatri 
Published: March 2019

The Indonesian is multi spoken languages society. Besides speaking with the official language (bahasa Indonesia), they also speaking in their own mother language. The use of local languages or the mother tongue is preferably as second language. Therefore, the acquisition of Indonesian, especially for Minangkabau society is strongly influenced by the structure of the first language. This is called as dialect or style. Slang or style can be seen from the lingual units that used by the speakers of the language. Lingual unit is a unit of language that carries meaning, both lexical and grammatical meaning. Unit lingual include morphemes, words, phrases, clauses, sentences, and discourse. In addition, there is another element which is the smallest unit in the language, segmental elements (phonemes) and supra-segmental elements (intonation). The results of the data analysis showed that there are some unit lingual speech marking Indonesian Minang people, namely: elements of segmental and supra-segmental elements, phatic, and sentence structure. In term of segmental elements, I have found six phonemes in Minangkabau language that affects Indonesian, phonemes are: /e/, /p/, /s/, /k/, and /j/. Moreover, in supra-segmental elements it appears that there tends to tone up the filler constituent predicate function. In declarative sentences, tone up there on the last syllable. In interrogative sentences, tone up tens to present in interrogative qualifiers. In imperative sentences, the intonation rising filler constituents tend be found in the predicate function, especially on the final syllable.