bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Assessment of Research Priorities to Dampen the Pendulum Swing of Burn Resuscitation
Authors: Burmeister David M , Smith Susan L , Muthumalaiappan Kuzhali , Hill David M , Moffatt Lauren T , Carlson Deborah L , Kubasiak John C , Chung Kevin K , Wade Charles E , Cancio Leopoldo C , Shupp Jeffrey W 
Published: December 2020

AbstractOn June 17 to 18, 2019, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn resuscitation in Washington, DC. The goal of the meeting was to identify and discuss novel research and strategies to optimize the process of burn resuscitation. Patients who sustain a large thermal injury (involving &gt;20% of the total body surface area [TBSA]) face a sequence of challenges, beginning with burn shock. Over the last century, research has helped elucidate much of the underlying pathophysiology of burn shock, which places multiple organ systems at risk of damage or dysfunction. These studies advanced the understanding of the need for fluids for resuscitation. The resultant practice of judicious and timely infusion of crystalloids has improved mortality after major thermal injury. However, much remains unclear about how to further improve and customize resuscitation practice to limit the morbidities associated with edema and volume overload. Herein, we review the history and pathophysiology of shock following thermal injury, and propose some of the priorities for resuscitation research. Recommendations include: studying the utility of alternative endpoints to resuscitation, reexamining plasma as a primary or adjunctive resuscitation fluid, and applying information about inflammation and endotheliopathy to target the underlying causes of burn shock. Undoubtedly, these future research efforts will require a concerted effort from the burn and research communities.
Dispersal patterns of a recovering brown bear (Ursus arctos) population in a human-dominated landscape
Authors: Karamanlidis Alexandros A , Kopatz Alexander , de Gabriel Hernando Miguel 
Published: December 2020

AbstractDespite increasing habitat fragmentation, large carnivore populations in parts of Europe have been recovering and expanding into human-dominated areas. Knowledge of animal dispersal patterns in such areas is important for their conservation, management, and coexistence with humans. We used genetic data based on 15 microsatellite markers from 312 individuals (98 females, 214 males) to assess kinship and dispersal patterns during the recovery and spatial expansion of a wild brown bear (Ursus arctos) population (2003–2010) in the human-dominated landscape of Greece. We hypothesized that bear dispersal in Greece was sex-biased, with females being more philopatric and males dispersing more frequently and over greater distances. Dispersal indeed was sex-biased, with males dispersing more frequently and farther than females. Overall, females were found to be philopatric; males also appeared to be philopatric, but to a lesser degree. However, a high proportion of females displayed dispersal behavior, which may be indicative of a pre-saturation stage of the population in that part of the country. Our results indicate that dispersal may be due to evading competition and avoiding inbreeding. We also documented long-distance dispersal of bears, which is considered to be indicative of a spatially expanding population. Our results highlight the value of using noninvasive genetic monitoring data to assess kinship among individuals and study dispersal patterns in human-dominated landscapes. Brown bears remain threatened in Greece; we therefore recommend systematic genetic monitoring of the species in combination with careful habitat management to protect suitable habitat (i.e., dispersal corridors) and ultimately ensure co-existence with humans and survival of brown bears in the country.
Associations Between Amplification (1q) and Prior Cancer in a Real-World De Novo Myeloma Cohort
Authors: Lamont Elizabeth B , Yee Andrew J , Goldberg Stuart L , Siegel David S , Norden Andrew D 
Published: December 2020

Abstract
Genomic biomarkers inform treatment in multiple myeloma (MM), making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset, we identified a cohort of 1769 patients with fluorescent in situ hybridization cytogenetic testing at diagnosis. Of the patients, 241 (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0.31 with prior cancer vs 0.24 without; 2-sided P = .02). No other MM translocations, amplifications, or deletions were associated with prior cancers. Amp(1q) and cancer history remained strongly associated in a logistic regression adjusting for patient demographic and disease attributes. The results merit follow-up regarding carcinogenic treatment effects and screening strategies for second malignancies. Broadly, the findings suggest that analyses of patient-level phenotypic-genomic real-world dataset may accelerate cancer research through hypothesis-generating studies.
Calcifying fibrous tumour—a rare cause of anaemia
Authors: Abd Kahar Nurul Nadhirah , Al-Mukhtar Ahmed 
Published: December 2020

Abstract
Calcifying fibrous tumour (CFT) is a rare benign tumour with non-specific anatomical distribution. We describe a case of a patient who presented with chronic generalised fatigue secondary to anaemia. Her symptoms did not improve while being on oral iron replacement therapy. Further endoscopic investigations were unremarkable. She had a computed tomography scan showing masses in the right pleural base and in the spleen. She then underwent splenic biopsy that only showed inflammatory changes. As her symptoms persisted, she was worked up for elective laparoscopic splenectomy during which she was found to have multiple peritoneal deposits. Biopsies were taken and the splenectomy was abandoned. The biopsies eventually showed changes consistent with CFT. This was conclusive for diagnosis of multifocal CFT.
Contested language in the making and unmaking of Western Sahara’s extractive economy
Authors: Irwin Randi L 
Published: December 2020

Abstract
This article considers the battle over resource extraction in the non-self-governing territory of Western Sahara. I analyse how the language of human rights has simultaneously been used by the Moroccan state to justify its extractive operations in the territory while Saharawi refugees use it to challenge these operations. Such competing invocations of human rights generate insight into how rights are made and re-made through configurations of populations, territory, markets, and regulations.
‘The Destiny of a Whole Race’: Identity, Race, and Politics in the Cold War Italian Performances of ‘Porgy and Bess’
Authors: Agugliaro Siel 
Published: December 2020

Abstract
In 1954–5, Porgy and Bess appeared for the first time in Italy in an all-Black production formally endorsed by the US State Department. Italian theatre administrators saw this production as an opportunity to sever any ideological connection with Fascism after decades of institutional support. At the same time, while Italian audiences and critics were often aware of the essentializing practices at the origins of Porgy and Bess, they relied on the stereotypical image of African American culture presented by the show to project their own experiences and political aspirations onto the opera’s subject and music. Drawing on primary sources, interviews, and the analysis of the earlier European reception of Porgy and Bess, this article argues that the success of the opera in Italy, rather than being determined by US diplomatic efforts, was a result of Italians’ need to redefine a sense of collective identity in a time of political transition.
Dose- and time-dependent tolerability and efficacy of organo-osmium complex FY26 and its tissue pharmacokinetics in hepatocarcinoma-bearing mice
Authors: Kumar Swati A , Needham Russell J , Abraham Kristin , Bridgewater Hannah E , Garbutt Lauren A , Xandri-Monje Helena , Dallmann Robert , Perrier Sebastien , Sadler Peter J , Lévi Francis 
Published: December 2020

Abstract
The organo-osmium complex [OsII(ɳ6-p-cym)(PhAzPy-NMe2)I]+ (FY26) exhibits promising in vitro antitumour activity against mouse hepatocarcinoma Hepa1–6 and other mouse or human cancer cell lines. Here, we drastically enhance water solubility of FY26 through the replacement of the PF6− counter-anion with chloride using a novel synthesis method. FY26⋅PF6 and FY26⋅Cl displayed similar in vitro cytotoxicity in two cancer cell models. We then show the moderate and late anticancer efficacy of FY26⋅PF6 and FY26⋅Cl in a subcutaneous murine hepatocarcinoma mouse model. Both efficacy and tolerability varied according to FY26 circadian dosing time in hepatocarcinoma tumour-bearing mice. Tumour and liver uptake of the drug were determined over 48 h following FY26⋅Cl administration at Zeitgeber time 6 (ZT6), when the drug is least toxic (in the middle of the light span when mice are resting). Our studies suggest the need to administer protracted low doses of FY26 at ZT6 in order to optimize its delivery schedule, for example through the use of chrono-releasing nanoparticles.
Distinguishing the effects of Ce nanoparticles from their dissolution products: identification of transcriptomic biomarkers that are specific for ionic Ce inChlamydomonas reinhardtii
Authors: Morel Elise , Dozois Jessica , Slaveykova Vera I , Wilkinson Kevin J 
Published: December 2020

AbstractCerium (Ce) is a rare earth element that is incorporated in numerous consumer products, either in its cationic form or as engineered nanoparticles (ENPs). Given the propensity of small oxide particles to dissolve, it is unclear whether biological responses induced by ENPs will be due to the nanoparticles themselves or rather due to their dissolution. This study provides the foundation for the development of transcriptomic biomarkers that are specific for ionic Ce in the freshwater alga, Chlamydomonas reinhardtii, exposed either to ionic Ce or to two different types of small Ce ENPs (uncoated, ∼10 nm, or citrate-coated, ∼4 nm). Quantitative reverse transcription PCR was used to analyse mRNA levels of four ionic Ce-specific genes (Cre17g.737300, MMP6, GTR12, and HSP22E) that were previously identified by whole transcriptome analysis in addition to two oxidative stress biomarkers (APX1 and GPX5). Expression was characterized for exposures to 0.03–3 µM Ce, for 60–360 min and for pH 5.0–8.0. Near-linear concentration–response curves were obtained for the ionic Ce and as a function of exposure time. Some variability in the transcriptomic response was observed as a function of pH, which was attributed to the formation of metastable Ce species in solution. Oxidative stress biomarkers analysed at transcriptomic and cellular levels confirmed that different effects were induced for dissolved Ce in comparison to Ce ENPs. The measured expression levels confirmed that changes in Ce speciation and the dissolution of Ce ENPs greatly influence Ce bioavailability.
AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production
Authors: Tsitsipatis Dimitrios , Grammatikakis Ioannis , Driscoll Riley K , Yang Xiaoling , Abdelmohsen Kotb , Harris Sophia C , Yang Jen-Hao , Herman Allison B , Chang Ming-Wen , Munk Rachel , Martindale Jennifer L , Mazan-Mamczarz Krystyna , De Supriyo , Lal Ashish , Gorospe Myriam 
Published: December 2020

Abstract
Mammalian circRNAs can influence different cellular processes by interacting with proteins and other nucleic acids. Here, we used ribonucleoprotein immunoprecipitation (RIP) analysis to identify systematically the circRNAs associated with the cancer-related protein AUF1. Among the circRNAs interacting with AUF1 in HeLa (human cervical carcinoma) cells, we focused on hsa_circ_0032434 (circPCNX), an abundant target of AUF1. Overexpression of circPCNX specifically interfered with the binding of AUF1 to p21 (CDKN1A) mRNA, thereby promoting p21 mRNA stability and elevating the production of p21, a major inhibitor of cell proliferation. Conversely, silencing circPCNX increased AUF1 binding to p21 mRNA, reducing p21 production and promoting cell division. Importantly, eliminating the AUF1-binding region of circPCNX abrogated the rise in p21 levels and rescued proliferation. Therefore, we propose that the interaction of circPCNX with AUF1 selectively prevents AUF1 binding to p21 mRNA, leading to enhanced p21 mRNA stability and p21 protein production, thereby suppressing cell growth.
Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study
Authors: Adolph Jonas E , Fleischhack Gudrun , Mikasch Ruth , Zeller Julia , Warmuth-Metz Monika , Bison Brigitte , Mynarek Martin , Rutkowski Stefan , Schüller Ulrich , von Hoff Katja , Obrecht Denise , Pietsch Torsten , Pfister Stefan M , Pajtler Kristian W , Witt Olaf , Witt Hendrik , Kortmann Rolf-Dieter , Timmermann Beate , Krauß Jürgen , Frühwald Michael C , Faldum Andreas , Kwiecien Robert , Bode Udo , Tippelt Stephan 
Published: December 2020

Abstract

Background
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.

Methods
Using data from the German multi-center E-HIT-REZ-2005 study, we examined the role of local therapy and the efficacy of chemotherapy with blockwise temozolomide (TMZ) in children and adolescents with recurrent ependymomas.

Results
Fifty-three patients with a median age of 6.9 years (1.25–25.4) at first recurrence and a median follow-up time of 36 months (2–115) were recruited. Gross- and near-total resection (GTR/NTR) were achieved in 34 (64.2%) patients and associated with a markedly improved 5-year overall survival (OS) of 48.7% vs. 5.3% in less than GTR/NTR. Radiotherapy showed no improvement in OS following complete resection (OS: 70 (CI: 19.9–120.1) vs. 95 (CI: 20.7–169.4) months), but an advantage was found in less than GTR/NTR (OS: 22 (CI: 12.7–31.3) vs. 7 (CI: 0–15.8) months). Following the application of TMZ, disease progression was observed in most evaluable cases (18/21). A subsequent change to oral etoposide and trofosfamide showed no improved response. PF-A EPN were most abundant in relapses (n = 27). RELA-positive EPN (n = 5) had a 5-year OS of 0%.

Conclusion
The extent of resection is the most important predictor of survival at relapse. Focal re-irradiation is a useful approach if complete resection cannot be achieved, but no additional benefit was seen after GTR/NTR. Longer-term disease stabilization (&gt;6 months) mediated by TMZ occurred in a small number of cases (14.3%).
Rolling-translated EGFR variants sustain EGFR signaling and promote glioblastoma tumorigenicity
Authors: Liu Yi , Li Zhongjun , Zhang Maolei , Zhou Huangkai , Wu Xujia , Zhong Jian , Xiao Feizhe , Huang Nunu , Yang Xuesong , Zeng Rong , Yang Lixuan , Xia Zhibo , Zhang Nu 
Published: December 2020

Abstract

Background
Aberrant epidermal growth factor receptor (EGFR) activation is observed in over 50% of cases of adult glioblastoma (GBM). Nevertheless, EGFR antibodies are ineffective in clinical GBM treatment, suggesting the existence of redundant EGFR activation mechanisms. Whether circular RNA (circRNA) encodes a protein involved in EGFR-driven GBM remains unclear. We reported an unexpected mechanism in which circular EGFR RNA (circ-EGFR) encodes a novel EGFR variant to sustained EGFR activation.

Method
We used RNA-seq, Northern blot, and Sanger sequencing to confirm the existence of circ-EGFR. Antibodies and a liquid chromatograph tandem mass spectrometer were used to identify circ-EGFR protein products. Lentivirus-transfected stable cell lines were used to assess the biological functions of the novel protein in vitro and in vivo. Clinical implications of circ-EGFR were assessed using 97 pathologically diagnosed GBM patient samples.

Results
The infinite open reading frame (iORF) in circ-EGFR translated repeating amino acid sequences via rolling translation and programmed −1 ribosomal frameshifting (-1PRF) induced out-of-frame stop codon (OSC), forming a polymetric novel protein-complex, which we termed rolling-translated EGFR (rtEGFR). rtEGFR directly interacted with EGFR, maintained EGFR membrane localization and attenuated EGFR endocytosis and degradation. Importantly, circ-EGFR levels correlated with the EGFR signature and predicted the poor prognosis of GBM patients. Deprivation of rtEGFR in brain tumor-initiating cells (BTICs) attenuated tumorigenicity and enhanced the anti-GBM effect.

Conclusion
Our findings identified the endogenous rolling-translated protein and provided strong clinical evidence that targeting rtEGFR could improve the efficiency of EGFR-targeting therapies in GBM.
Extracting Money from Causal Decision Theorists
Authors: Oesterheld Caspar , Conitzer Vincent 
Published: December 2020

Abstract
Newcomb’s problem has spawned a debate about which variant of expected utility maximisation (if any) should guide rational choice. In this paper, we provide a new argument against what is probably the most popular variant: causal decision theory (CDT). In particular, we provide two scenarios in which CDT voluntarily loses money. In the first, an agent faces a single choice and following CDT’s recommendation yields a loss of money in expectation. The second scenario extends the first to a diachronic Dutch book against CDT.
The effect of LyPRP/collagen composite hydrogel on osteogenic differentiation of rBMSCs
Authors: Chen Manyu , Liu Quanying , Xu Yang , Wang Yuxiang , Han Xiaowen , Wang Zhe , Liang Jie , Sun Yong , Fan Yujiang , Zhang Xingdong 
Published: December 2020

Abstract
Although platelet-rich plasma (PRP) plays a significant role in the orthopedic clinical application, it still faces two major problems, namely, uncontrollable factors release, frequent preparation and extraction processes as well as the inconvenient form of usage. To overcome these shortcomings, freeze-dried PRP (LyPRP) was encapsulated into bioactive Col I hydrogel to induce osteogenic differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). And PRP/Col І composite hydrogel was prepared as a control. Compared with Col І hydrogel, the introduction of platelets significantly improved the mechanical properties of hydrogels. Meanwhile, platelets were evenly distributed in the composite hydrogels network. The sustainable release of related factors in the composite hydrogels could last for more than 14 days to maintain its long-term biological activity. Further cell experiments confirmed that PRP and LyPRP could effectively alleviate the contraction of collagen hydrogel in vitro, and promote the adhesion, proliferation and osteogenesis differentiation of rBMSCs. The results of osteogenic gene expression indicated that the 10% LyPRP/Col І composite hydrogel could facilitate the early expression of BMP-2 and late osteogenic associated protein formation with higher expression of alkaline phosphatase and Osteocalcin (OCN). These results might provide new insights for the clinical application of 10% LyPRP/Col І composite hydrogel as practical bone repair injection.
Effects of multilevel policy mix of public R&D subsidies: Empirical evidence from Japanese local SMEs
Authors: Okamuro Hiroyuki , Nishimura Junichi 
Published: December 2020

Abstract
Regional innovation policies have been implemented in several countries. In Japan, controlled decentralization of traditionally centralized innovation policy is ongoing, so that we can observe multilevel policy mix of public R&D (research and development) subsidies by national, prefecture, and city governments. However, empirical studies on multilevel R&D support using panel data and considering municipality level have been scarce. Based on original survey data and financial data of manufacturing small and medium enterprises (SMEs), we estimate their total factor productivity (TFP) and empirically investigate the effects of public R&D subsidies by national, prefecture, and city governments. We employ firm-level fixed-effect panel estimation in order to control for the effects of any unobservable time-invariant factors. We find that multilevel subsidies (especially those involving city subsidies) complementarily and persistently increase recipients’ TFP. These results suggest significant advantages of multilevel policy mix, especially those involving city subsidies.
Effect of the new dual orexin receptor antagonist daridorexant on nighttime respiratory function and sleep in patients with mild and moderate obstructive sleep apnea
Authors: Boof Marie-Laure , Dingemanse Jasper , Lederer Katharina , Fietze Ingo , Ufer Mike 
Published: December 2020

Abstract
In this randomized, double-blind, placebo-controlled, two-period crossover study, the effect of the dual orexin receptor antagonist daridorexant was evaluated on nighttime respiratory function and sleep in 28 patients with mild and moderate obstructive sleep apnea (OSA). In each period, 50 mg daridorexant or placebo was administered every evening for 5 days. The primary endpoint was apnea/hypopnea index (AHI) during total sleep time (TST) after the last dosing. Other endpoints included peripheral oxygen saturation (SpO2), sleep duration, latency to persistent sleep (LPS), wake after sleep onset (WASO), and sleep efficiency index (SEI). Pharmacokinetics, safety, and tolerability were also assessed. The mean treatment difference for AHI during TST (i.e. daridorexant − placebo) after the last dosing was 0.74 events/hour (90% confidence interval [CI]: –1.43, 2.92). The corresponding treatment difference for SpO2 during TST was 0.16% [90% CI: –0.21, 0.53]. Overall, there was no clinically relevant effect of daridorexant on AHI or SpO2-related data after single and repeated dosing irrespective of sleep phase (i.e. rapid eye movement [REM] vs non-REM). Moreover, after single and repeated dosing, daridorexant prolonged TST by 39.6 minutes (90% CI: 16.9, 62.3) and 38.8 minutes (19.7, 57.9), respectively, compared with placebo and favorably modulated other sleep-related endpoints (i.e. increased SEI, decreased WASO, and shortened LPS). It attained expected plasma concentrations and was well tolerated in patients with mild and moderate OSA.
These results indicate that single and repeated doses of 50 mg daridorexant do not impair nighttime respiratory function and improve sleep in patients with mild and moderate OSA.
Clinical Trial Registration: ClinicalTrials.gov NCT03765294. A study to investigate the effects of ACT-541468 on nighttime respiratory function in patients with mild to moderate obstructive sleep apnea. https://clinicaltrials.gov/ct2/show/ NCT03765294.