bluuebunny/crossref_metadata_2025_split huggingface dataset:
The New Israel: The evolution of the idea and image among Christian nations
Authors: Malach Assaf 
Published: February 2020

AbstractThis article deals with the use made by Christian people of the image of a chosen people for national and political purposes, while identifying a specific Christian nation or kingdom as the “New Israel.” It begins by describing the idea of “New Israel” as a pan‐Christian idea that underwent a fundamental change when its use began with reference to a specific nation. The article continues with a detailed mapping of the phenomenon in Ethiopian Christianity, in the Catholic world in the Middle Ages, in the Russian Orthodox world, and in the Protestant countries in the early days of the modern era. The article describes the broad context of the phenomenon in the framework of ethnocentric imagery in different cultures and the continuation of the research required for its full description.This phenomenon is interesting because it indicates the importance that many people attributed in the premodern period to the formulation of a national narrative and the centrality of religion in formulating a national narrative during this period. It emphasizes the political inspiration that Europe drew from the Bible in the formulation of national narratives, as well as the prominence of the national idea in the Bible itself, which made it an accessible source of inspiration for national ideas of Christian people.
Orally administered mixed carotenoids protect human skin against ultraviolet A‐induced skin pigmentation: A double‐blind, placebo‐controlled, randomized clinical trial
Authors: Baswan Sudhir M. , Marini Alessandra , Klosner Allison E. , Jaenicke Thomas , Leverett Jesse , Murray Mary , Gellenbeck Kevin W. , Krutmann Jean 
Published: February 2020

AbstractBackgroundPhotoprotection of human skin is determined as the capacity of sunscreens to prevent ultraviolet (UV) B radiation‐induced erythema and UVA radiation‐induced pigmentation. It is unequivocal that, in addition to sunscreens, oral supplementation with carotenoids can protect human skin against UVB radiation‐induced erythema. It is not known if this is also the case for UVA radiation‐induced pigmentation.ObjectiveTo clinically evaluate the photoprotective effects of daily supplementation with carotenoids against UVA radiation‐induced pigmentation.MethodsIn this double‐blind, placebo‐controlled trial, 60 subjects (Fitzpatrick types II‐IV) were randomized to receive Nutrilite™ Multi Carotene supplement or placebo for 12 weeks. UVB‐induced minimal erythemal dose (MED), UVA‐induced minimal persistent pigmentation dose (MPPD) and skin carotenoid levels were measured at baseline, 4, 8, and 12 weeks of intervention. Skin color was evaluated by expert clinical graders and by colorimetry. Carotenoid levels in the skin were measured by the Biozoom® device.ResultsIn the intervention group, a significant increase in comparison with the placebo group was observed in (a) skin carotenoid levels, (b) UVB‐induced MED, and (c) UVA‐induced MPPD values obtained by colorimetry.ConclusionDaily supplementation with carotenoids protects human skin against both UVB‐induced erythema and UVA‐induced pigmentation.
Experimental boundary conditions of reinstatement‐induced return of fear in humans: Is reinstatement in humans what we think it is?
Authors: Sjouwerman Rachel , Lonsdorf Tina B. 
Published: February 2020

AbstractExperimental paradigms used to study reinstatement of fear in humans are characterized by procedural heterogeneity. Reinstatement protocols involve unexpected (re)‐presentations of the unconditioned stimulus (USs) after fear extinction training. Here, we address the number of reinstatement USs administered as a potential boundary condition that may explain divergent findings in the field. A sample of 171 participants is exposed to a fear acquisition training, immediate extinction training, and reinstatement test experiment. Three groups differing in the number of reinstatement US are employed: one (n = 57) or four (n = 55) in experimental groups and zero (n = 59) in the control group. We adopt Bayesian statistical approaches beyond classical null hypothesis significance testing (NHST) to qualify evidence for or against this potential methodological boundary condition in reinstatement‐induced return of fear. Startle potentiation to the reinstatement administration context was increased for the RI–USone compared to the RI–USzero group, supporting the role of context conditioning in reinstatement. This effect was weaker in the RI–USfour group. This, however, did not transfer to responding to conditioned stimuli during the return of fear‐test: no evidence for an effect of the number of reinstatement USs (zero, one, four) was observed in behavioral or physiological measures. In sum, our results speak against the number of reinstatement USs as a potential boundary condition in experimentally induced return of fear in humans. This may challenge what we think we know about the reinstatement phenomenon in humans and call for critical reconsideration of paradigms as well as mechanisms that may underlie some reinstatement effects in the literature.
The association between serum adipocyte fatty acid–binding protein and 3-month disability outcome after aneurysmal subarachnoid hemorrhage
Authors: Luo Yong-Gang , Han Bing , Sun Tong-Wen , Liu Xianzhi , Liu Jun , Zhang Jun 
Published: February 2020

AbstractBackgroundAdipocyte fatty acid–binding protein (FABP4) is an adipokine that plays an important role in development of cardiovascular and metabolic diseases. The aim of this study was to assess the 3-month prognostic value of serum levels of FABP4 in Chinese patients with aneurysmal subarachnoid hemorrhage (aSAH) on hospital admission.MethodsThis was a prospective observational study from a stroke treatment center in Zhengzhou, China. From October 2016 to May 2018, patients with aSAH who were hospitalized within 24 h were included. In addition, 202 age- and gender-matched healthy volunteers were assigned to the healthy control group. At admission, serum levels of FABP4 were measured, and patients’ characteristics, Hunt–Hess grade, and modified Fisher grade evaluated. At 3-month follow-up, functional outcome (Glasgow Outcome Scale score; dichotomized as poor [score 1–3] or good [score 4–5]) and all-cause mortality were recorded. Univariate and multivariate logistic regression models were used to investigate the association of FABP4 with the two endpoints.ResultsA total of 418 patients with aSAH were included in this study. The median age was 58 years (interquartile range, 49–66 years), and 57.9% were women. FABP4 serum levels were related to Hunt–Hess score (r[Spearman] = 0.381;P < 0.001). Patients with a poor outcome and non-survivors had significantly increased serum FABP4 levels on admission (P < 0.001 for all). In multivariate logistic regression analysis, FABP4 was an independent predictor of poor outcome and mortality, with increased risks of 7% (odds ratios 1.07, 95% confidence interval [CI] 1.02–1.13;P = 0.001) and 5% (odds ratio 1.05, 95% CI, 1.01–1.12;P = 0.003), respectively. Receiver operating characteristics to predict functional outcome and mortality were significantly different between conventional risk factors (difference area under the curve 0.024, 95% CI 0.018–0.032) and FABP4 plus conventional risk factors (area under the curve 0.015, 95%CI 0.011–0.020). After FABP4 was added to the existing risk factors, mortality was better reclassified and was associated with the net reclassification improvement statistic (P = 0.009), while poor outcome was better reclassified and associated with both the integrated discrimination improvement and net reclassification improvement statistics (P < 0.05 for all).ConclusionsElevated serum FABP4 levels were related to poor outcome and mortality in a cohort of patients with aSAH.
Niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD): Correlative measures of tumor response in phase II GALAHAD study.
Authors: Smith Matthew Raymond , Fizazi Karim , Sandhu Shahneen Kaur , Kelly William Kevin , Efstathiou Eleni , Lara Primo , Yu Evan Y. , George Daniel J. , Chi Kim N. , Saad Fred , Summa Jason , Freedman Jamie M. , Mason Gary , Espina Byron M. , Zhu Eugene , Ricci Deborah S. , Snyder Linda A. , Simon Jason S. , Cheng Shinta , Scher Howard I. 
Published: February 2020

118 Background: Niraparib, a highly potent and selective poly (ADP-ribose) polymerase inhibitor (PARPi) received breakthrough designation by US FDA for treatment of pts with BRCA1,2 mutant mCRPC who progressed on taxane and androgen receptor-targeted therapy. Circulating tumor cells (CTC) detection associates with poor outcomes, with declining counts consistent with improved survival [1,2]. Methods: GALAHAD study assessed niraparib (300 mg daily) in pts with mCRPC+DRD (NCT02854436). Patients with non-measurable soft tissue disease by RECIST 1.1 were required to have a baseline CTC count ≥1 cell/7.5 mL blood. CTC response was defined as CTC conversion to <5 for pts with baseline CTC≥5 and CTC drop to 0 post-baseline for pts with ≥1 baseline CTC. Alkaline phosphatase (ALP) was collected at each monthly cycle. Results: For primary efficacy population of pts with BRCA1/2 mutations, the objective response rate (ORR) by RECIST 1.1 criteria was 41.4%. CTC response rates for this population were as high as ORR regardless of measurability (Table). Time to CTC response for each CTC responder will be shown. Radiographic progression-free survival (rPFS) durations were similar for patients with a measurable disease response and patients with CTC conversion. Median duration of treatment for responders of any type was 6.7mo (range: 2–27). DRD status, both BRCA and non- BRCA, for each responder will also be discussed. Trends in disease burden and markers of bone metabolism will also be quantitatively explored including 24% pts who were on treatment for at least one cycle who had ≥25% decreased unfractionated ALP from baseline. Conclusions: Niraparib showed clinical activity with CTC response and decline in ALP levels in mCRPC pts having biallelic BRCA mutations, which further supports its recent breakthrough designation. Clinical trial information: NCT02854436. [Table: see text]
Adenosine receptor blockade with ciforadenant +/- atezolizumab in advanced metastatic castration-resistant prostate cancer (mCRPC).
Authors: Harshman Lauren Christine , Chu Michael , George Saby , Hughes Brett Gordon Maxwell , Carthon Bradley Curtis , Fong Lawrence , Merchan Jaime R. , Kwei Long , Hotson Andrew N. , Mobasher Mehrdad , Miller Richard A. 
Published: February 2020

129 Background: Adenosine, generated by the ectonucleotidase CD73, mediates immunosuppression within the tumor microenvironment by triggering adenosine 2A receptors (A2AR) on immune cells. Tumor CD73 expression may be prognostic in prostate cancer. We evaluated the clinical activity of adenosine blockade using A2AR antagonist, ciforadenant, with or without the anti-PDL-1 antibody, atezolizumab (atezo), in advanced mCRPC patients (pts) in an ongoing phase 1 trial. Methods: Eligibility required measurable disease and up to 5 prior systemic therapies. Prior anti- PD-(L)1 was allowed. Ciforadenant was administered orally BID as monotherapy at 50-200mg or 100mg in combination with atezo 840mg IV Q 2 weeks (wks). Safety and efficacy were evaluated by CTCAE4, RECIST1.1 and PCWG2. Serum was obtained for measurement of cytokines. Results: Of 33 enrolled pts, 10 received ciforadenant monotherapy and 23 in combination with atezo. As of 10/21/19, 14 pts are evaluable for response and described further. Median prior therapies is 3 (range 2-6) with median follow-up 10.8 (4-33) wks. Metastatic burden included 4 node only, 2 bone plus node, and 8 visceral metastases. Five pts experienced tumor regression: 2 ciforadenant monotherapy (tumor reductions 12%, 17%); and 3 combination (tumor reductions 4%, 27%, 42%). The pt with a partial response had PSA decline from 98 ng/mL to <1. Eight pts had stable disease (SD) for a clinical benefit rate (SD + PR) of 8/14 (57%). Median duration of disease control was 24 wks. Study treatment was well tolerated with two Gr3/4 adverse events (AEs) of fatigue (1) and anorexia (1). The most common Gr1/2 AEs were fatigue and nausea. Serum TNFα levels increased by 4-8 wks on therapy in 12/13 pts. Baseline levels of soluble VCAM-1, which has been implicated in metastatic spread/more aggressive disease, were higher in pts with tumor regression (771 ± 109 ng/mL, n=4) than pts with tumor growth (544 ± 62 ng/mL, n=5, p<0.05). Conclusions: Results from this phase 1 study show mCRPC can be sensitive to A2AR blockade with ciforadenant. Cytokine changes provide evidence of treatment-induced inflammatory response, which may predict efficacy. Data on all 33 enrolled pts will be presented. Clinical trial information: NCT02655822.
Feasibility and oncologic outcome of salvage surgery in isolated seminal vesical remnants after radical prostatectomy.
Authors: Pfister David , Haidl Friederike , Nestler Tim , Paffenholz Pia , Heidenreich Axel 
Published: February 2020

137 Background: Improved imaging modalities identify metastatic prostate cancer earlier. Atypical and oligometastatic disease is identified more often. Thus a more individual treatment approach in oligometastatic prostate cancer is getting more popular. We demonstrate our results in recurrent disease in seminal vesical remnants after radical prostatectomy and radiotherapy. Methods: A total of 33 patients underwent open resection of locoregional recurrence in seminal vesicals. In case of suspicious 68Ga-PSMA-PET findings in the small pelvis an additional ipsilateral lymph node dissection was performed in 10 patients. 11 patients already received hormone treatment fulfilling the definition of castration resistant prostate cancer. Age, PSA-DT, PSA, time to recurrence after primary treatment resection status were used in a uni and multivariate-cox regression analysis for biochemical relapse after surgery. Results: Median patient age at time of salvage surgery was 70(57-77) years. Median PSA and PSA-DT was 2.79(0.4-61.54)ng/ml and 5.4(1.6-20.1)months respectively. Median surgical time and hospital stay was 132 (75-313)min and 5.5(4-13)days. Median progression-free survival was 29 (8-47) months. After a mean follow-up of 22 months (3-68) months three patients died 8, 14, and 40 months after salvage surgery. In a univariable cox-regression analyses age at time of surgery, preoperative PSA and the time from primary treatment to salvage surgery have been identified as significant parameters for biochemichal relapse. Only the interval from primary to salvage surgery was significant with a Hazard ratio of 1.008 (95%-CI 1.001-1.015, p=0,018) in multivariate analysis. 4 adjunctive surgeries (Ureterovericoneostomy n=3 and one nephrectomy) were needed due to local progressive disease. Conclusions: Seminal vesicle resection is feasible with no significant intra and postoperative complications even in CRPC. Although there is a good median progression-free survival after 5 years almost all patients had biochemical or systemic relapse. Salvage surgery must be seen as prevention for local symptoms, to our experience most often postrenal ipsilateral obstruction.
Intermediate atypical carcinoma (IAC): A discrete subtype of metastatic castration-resistant prostate cancer (mCRPC) suggesting that treatment-associated small cell/neuroendocrine prostate cancer (t-SCNC) may evolve from mCRPC adenocarcinoma (adeno)—Results from the SU2C/PCF/AACR West Coast Prostate Cancer Dream Team (WCDT).
Authors: Small Eric Jay , Aggarwal Rahul Raj , Friedl Verena , Weinstein Alana , Thomas George V. , True Lawrence D. , Foye Adam , Beer Tomasz M. , Rettig Matthew , Gleave Martin , Evans Christopher P. , Alumkal Joshi J. , Reiter Robert Evan , Lara Primo , Chi Kim N. , Feng Felix Y , Bailey Adina , Stuart Josh , Huang Jiaoti 
Published: February 2020

158 Background: A subset of mCRPC patients (pts) that develop resistance to next-gen androgen signaling inhibitors are subsequently found to harbor t-SCNC. We have undertaken a longitudinal prospective biopsy (bx) study to clinically and molecularly characterize these pts. Methods: Eligible pts underwent an image-guided mCRPC bx at one of 5 WCDT centers. Tissue was both frozen and formalin fixed/paraffin embedded (FFPE). FFPE tissue was used for targeted next generation sequencing (NGS) and independent pathologic review by 3 pathologists. Frozen specimens underwent laser capture micro-dissection prior to RNA sequencing (seq). Machine learning was used to derive histology-specific expression signatures. Linear Discriminant Analysis (LDA) was applied to the RNA seq data from the first 131 bx using 3 observed histologic subtypes as labels to test for an intermediate subtype. Results: Of 391 mCRPC metastasis (53% bone, 26% node, 12% liver, 9% other soft tissue), 295(75%) yielded cancer. Overall, 89% of the bx contained a single histologic subtype: pure adeno in 156(53%); pure t-SCNC in 35(12%). A novel morphologically distinct subtype, IAC, with features of both tSCNC and adeno was seen in 72(24%). Samples comprised of two subtypes made up 32(11%) of all bx. Overall, 50(17%) of bx had a t-SCNC component. TP53 and/or RB1 loss of function variants were significantly more frequent in t-SCNC. NGS revealed no difference between adeno and IAC. LDA classified IAC as intermediate between adeno and t-SCNC 93% of the time, across 100 bootstrap replicates, significantly better than the 33% expected by chance (p <10−17). Conclusions: Nearly half of mCRPC bx exhibit non-adeno features with t-SCNC found in 17%. IAC is a reproducible mCRPC histologic subtype found in 24% of bx, with a gene expression signature that is intermediate to adeno and t-SCNC, and targeted NGS results similar to adeno. Understanding the role of IAC in disease evolution and resistance is critical for improving outcomes in mCRPC. Clinical trial information: NCT02432001.
Radiotherapy (RT) guided by ultra‐small superparamagnetic iron oxide (USPIO)-contrast MRI staging for patients with advanced or recurrent prostate cancer.
Authors: Li Yun Rose , Dattoli Michael J. , Barentsz Jelle , Roach Mack 
Published: February 2020

218 Background: Aggressive treatment of oligometastatic PC may prolong survival in selected patients. USPIO-contrast MRI is potentially more sensitive in detecting early lymph node (LN) metastases than PET. Methods: This retrospective study explores the safety and utility of USPIO-guided RT in 69 patients with advanced/recurrent PC treated at 2 US institutions. All USPIO-MRIs were completed at RadboudUMC and interpreted by expert radiologists. Age, Stage, Gleason score, PSA, prior therapy, duration of androgen-deprivation (ADT), cause of death, details of RT, and adverse events (AEs) were collected by chart review. Biochemical recurrence (BCR) was defined as PSA Nadir plus 2.0 (RT) or PSA>0.2 (radical prostatectomy, RP). Patients received external beam radiation (RT) to involved nodal basins (+/-prostate/prostate bed) with either a simultaneous integrated or sequential boost to USPIO(+) nodes. All patients received >6 months of ADT. Overall (OS) and BCR free-survival (BCRFS) were calculated using Cox-PH models in R. Results: Between 2007-18, 69 patients with de novo or recurrent PC were found to have USPIO(+) LNs and received USPIO-guided RT; median age was 62. The majority of patients presented after BCR following RP (N=28), definitive RT (N=27) or RP and post-op RT (N=6). Prior to USPIO-MRI, 20/69 patients had cN1 disease based on abdominal-pelvic CT/MRI, Bone Scan, Prostascint-scan, and F18 Choline, Axumin or PSMA PET/CT. The mean(median)USPIO(+) LNs was 5.2(3) Range=[1-32]. Patients had (+)pelvic (95%), para-aortic (43%), and/or peri-rectal LNs (19%). At median follow up of 29.5(44.6) Range=[5-127] months, OS was 58/69 (84%) and 11/11 patients died of PC. At last follow up, 40 patients remained BCR-free (BCRFS not reached). The median time to BCR (N=29) was 25.9 months after USPIO-guided RT. For patients with follow-up imaging, recurrences were predominantly out-of-field (outside of elective LN fields or in osseous sites). No patients experienced >CTCAE grade 2 AEs. Conclusions: In this cohort of 69 patients with predominantly recurrent PC, USPIO-directed RT was well-tolerated, feasible and resulted in encouraging biochemical control rates.
Impact of 68Ga-PSMA-11 PET on the management of biochemically recurrent prostate cancer in a prospective single-arm clinical trial.
Authors: Fendler Wolfgang , Ferdinandus Justin , Calais Jeremie , Eiber Matthias , Flavell Robert R. , Mishoe Ashley , Feng Felix Y , Nguyen Hao Gia , Reiter Robert Evan , Rettig Matthew , Gartmann Jeannine , Smith Raven , Small Eric Jay , Slavik Roger , Carroll Peter , Herrmann Ken , Czernin Johannes , Hope Thomas ,   The PSMA PET Reader Group
Published: February 2020

292 Background: Prostate-specific membrane antigen ligand positron emission tomography (PSMA PET) induced management changes in up to every second patient in smaller clinical trials. We aim to determine the impact of 68Ga-PSMA-11 PET/CT on management of biochemically recurrent prostate cancer in a large prospective cohort. Methods: We report management changes following PSMA PET, a secondary endpoint of a prospective multicenter trial in men with prostate cancer biochemical recurrence (NCT02940262 and NCT03353740). Pre-PET, Post-PET and Post-Treatment Questionnaires were sent to referring physicians recording working clinical summaries, intended and implemented therapeutic and diagnostic management. Results: Intended management change occurred in 260/382 (68%) patients. Intended change was considered major in 176/382 (46%) patients. Management pathway aligned with PET findings, i.e. change towards local/focal therapy for locoregional disease (54/126 patients, 44%) and towards systemic therapy or combination approaches for metastatic disease (106/153 patients, 69%). Intended management was implemented in 160/206 (78%) patients. Perceived site of disease was unknown in 259/382 (68%) patients before and 111/382 (29%) patients after PSMA PET. A total of 150 intended diagnostic tests, mostly CT (n=43, 29%) and bone Scans/NaF-PET (n=52, 35%), were prevented by PSMA PET. A total of 73 tests, mostly biopsies (n=44, 60%) requested by the study protocol, were triggered. Conclusions: Disease localization by PSMA PET translated into management changes in more than half of patients with biochemical recurrence of prostate cancer. More than twice as many diagnostic tests were prevented than triggered following PET. Clinical trial information: NCT02940262 and NCT03353740.