bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA-Binding Protein HuR Regulates Both Mutant and Wild-Type IDH1 in IDH1-Mutated Cancer
Authors: Zarei Mahsa , Lal Shruti , Vaziri-Gohar Ali , O'Hayer Kevin , Gunda Venugopal , Singh Pankaj K. , Brody Jonathan R. , Winter Jordan M. 
Published: September 2018

Abstract

Isocitrate dehydrogenase 1 (IDH1) is the most commonly mutated metabolic enzyme in human malignancy. A heterozygous genetic alteration, arginine 132, promotes the conversion of α-ketoglutarate to D-2-hydroxyglutarate (2-HG). Although pharmacologic inhibitors of mutant IDH1 are promising, resistance mechanisms to targeted therapy are not understood. Additionally, the role of wild-type IDH1 (WT.IDH1) in cancer requires further study. Recently, it was observed that the regulatory RNA-binding protein, HuR (ELAVL1), protects nutrient-deprived cancer cells without IDH1 mutations, by stabilizing WT.IDH1 transcripts. In the present study, a similar regulatory effect on both mutant (Mut.IDH1) and WT.IDH1 transcripts in heterozygous IDH1-mutant tumors is observed. In ribonucleoprotein immunoprecipitation assays of IDH1-mutant cell lines, wild-type and mutant IDH1 mRNAs each bound to HuR. Both isoforms were profoundly downregulated at the mRNA and protein levels after genetic suppression of HuR (siRNAs or CRISPR deletion) in HT1080 (R132C IDH1 mutation) and BT054 cells (R132H). Proliferation and invasion were adversely affected after HuR suppression and metabolomic studies revealed a reduction in Pentose Phosphate Pathway metabolites, nucleotide precursors, and 2-HG levels. HuR-deficient cells were especially sensitive to stress, including low glucose conditions or a mutant IDH1 inhibitor (AGI-5198). IDH1-mutant cancer cells were rescued by WT.IDH1 overexpression to a greater extent than Mut.IDH1 overexpression under these conditions. This study reveals the importance of HuR's regulation of both mutant and wild-type IDH1 in tumors harboring a heterozygous IDH1 mutation with implications for therapy.

Implications:
This study highlights the HuR–IDH1 (mutant and wild-type IDH1) regulatory axis as a critical, actionable therapeutic target in IDH1-mutated cancer, and incomplete blockade of the entire HuR–IDH1 survival axis would likely diminish the efficacy of drugs that selectively target only the mutant isoenzyme.
Genome-Informed Targeted Therapy for Osteosarcoma
Authors: Sayles Leanne C. , Breese Marcus R. , Koehne Amanda L. , Leung Stanley G. , Lee Alex G. , Liu Heng-Yi , Spillinger Aviv , Shah Avanthi T. , Tanasa Bogdan , Straessler Krystal , Hazard Florette K. , Spunt Sheri L. , Marina Neyssa , Kim Grace E. , Cho Soo-Jin , Avedian Raffi S. , Mohler David G. , Kim Mi-Ok , DuBois Steven G. , Hawkins Douglas S. , Sweet-Cordero E. Alejandro 
Published: September 2018

Abstract

Osteosarcoma is a highly aggressive cancer for which treatment has remained essentially unchanged for more than 30 years. Osteosarcoma is characterized by widespread and recurrent somatic copy-number alterations (SCNA) and structural rearrangements. In contrast, few recurrent point mutations in protein-coding genes have been identified, suggesting that genes within SCNAs are key oncogenic drivers in this disease. SCNAs and structural rearrangements are highly heterogeneous across osteosarcoma cases, suggesting the need for a genome-informed approach to targeted therapy. To identify patient-specific candidate drivers, we used a simple heuristic based on degree and rank order of copy-number amplification (identified by whole-genome sequencing) and changes in gene expression as identified by RNA sequencing. Using patient-derived tumor xenografts, we demonstrate that targeting of patient-specific SCNAs leads to significant decrease in tumor burden, providing a road map for genome-informed treatment of osteosarcoma.

Significance:
Osteosarcoma is treated with a chemotherapy regimen established 30 years ago. Although osteosarcoma is genomically complex, we hypothesized that tumor-specific dependencies could be identified within SCNAs. Using patient-derived tumor xenografts, we found a high degree of response for “genome-matched” therapies, demonstrating the utility of a targeted genome-informed approach.
This article is highlighted in the In This Issue feature, p. 1
FAP Delineates Heterogeneous and Functionally Divergent Stromal Cells in Immune-Excluded Breast Tumors
Authors: Cremasco Viviana , Astarita Jillian L. , Grauel Angelo L. , Keerthivasan Shilpa , MacIsaac Kenzie , Woodruff Matthew C. , Wu Michael , Spel Lotte , Santoro Stephen , Amoozgar Zohreh , Laszewski Tyler , Migoni Sara Cruz , Knoblich Konstantin , Fletcher Anne L. , LaFleur Martin , Wucherpfennig Kai W. , Pure Ellen , Dranoff Glenn , Carroll Michael C. , Turley Shannon J. 
Published: September 2018

Abstract
Cancer-associated fibroblasts (CAFs) are generally associated with poor clinical outcome. CAFs support tumor growth in a variety of ways and can suppress antitumor immunity and response to immunotherapy. However, a precise understanding of CAF contributions to tumor growth and therapeutic response is lacking. Discrepancies in this field of study may stem from heterogeneity in the composition and function of fibroblasts in the tumor microenvironment. Furthermore, it remains unclear whether CAFs directly interact with and suppress T cells. Here, mouse and human breast tumors were used to examine stromal cells expressing fibroblast activation protein (FAP), a surface marker for CAFs. Two discrete populations of FAP+ mesenchymal cells were identified on the basis of podoplanin (PDPN) expression: a FAP+PDPN+ population of CAFs and a FAP+PDPN− population of cancer-associated pericytes (CAPs). Although both subsets expressed extracellular matrix molecules, the CAF transcriptome was enriched in genes associated with TGFβ signaling and fibrosis compared with CAPs. In addition, CAFs were enriched at the outer edge of the tumor, in close contact with T cells, whereas CAPs were localized around vessels. Finally, FAP+PDPN+ CAFs suppressed the proliferation of T cells in a nitric oxide–dependent manner, whereas FAP+PDPN− pericytes were not immunosuppressive. Collectively, these findings demonstrate that breast tumors contain multiple populations of FAP-expressing stromal cells of dichotomous function, phenotype, and location.
Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease
Authors: Scheinert Dierk , Micari Antonio , Brodmann Marianne , Tepe Gunnar , Peeters Patrick , Jaff Michael R. , Wang Hong , Schmahl Randy , Zeller Thomas ,   on behalf of the IN.PACT Global Study Investigators
Published: September 2018

Background
The IN.PACT Global Study was an international prospective single-arm clinical trial to evaluate the safety and effectiveness of a drug-coated balloon in the treatment of atherosclerotic disease of the superficial femoral and/or popliteal arteries (P1–P3) in subjects with intermittent claudication and/or rest pain. Prespecified subjects were selected for core-laboratory–adjudicated duplex ultrasound imaging, including a subcohort with long lesions (≥15 cm).

Methods and Results
Subjects were followed for 12 months. The primary safety end point was a composite of freedom from device- and procedure-related mortality through 30 days and freedom from major target limb amputation and clinically-driven target vessel revascularization through 12 months. An independent Clinical Events Committee adjudicated all adverse events. The primary effectiveness end point was primary patency at 12 months (by duplex ultrasound). The long lesion imaging cohort had 157 subjects (164 lesions). Mean lesion length was 26.40±8.61 cm. Provisional stents were implanted in 39.4% (63/160) of lesions. Primary patency by Kaplan-Meier estimate was 91.1%, and freedom from clinically-driven target lesion revascularization was 94.2% at 12 months. The primary safety composite end point was achieved by 94.0% (126/134) of subjects. There were no device- or procedure-related deaths or major target limb amputations.

Conclusions
The IN.PACT Admiral drug-coated balloon was safe and highly effective at 12 months after treatment in a rigorous independently adjudicated analysis of real-world subjects with lesions ≥15 cm in the superficial femoral and/or popliteal arteries (P1–P3).

CLINICAL TRIAL REGISTRATION

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01609296.
William of Ockham on Future Contingency
Authors: Øhrstrøm Peter , Jakobsen David 
Published: September 2018

Abstract
In his philosophy, William of Ockham (1285-1347) offered an important and detailed response to the classical argument from the truth of a statement regarding the future to the necessity (unpreventability) of the statement. In this paper, Ockham’s solution and the possible formalisation of it are discussed in terms of modern tense and modal logic. In particular, the famous branching time formalisation suggested by A. N. Prior (1914-19) is discussed. Weaknesses and problems with this suggestion are pointed out, and an alternative formalisation of Ockham’s solution without the use of branching time is presented.
Decolonial Thinking and the Quest for Decolonising Human Rights
Authors: Barreto José-Manuel 
Published: September 2018

Abstract
This article offers an answer to the questions about what does it mean to think decolonially, and of how it is possible to decolonise human rights. It describes decolonial thinking as a material dialectics of a critique of Eurocentrism, a rescue of Third-World perspectives, and a dialogue between the two. It then takes this threefold movement of consciousness and political action to the field of human rights, and thematises some exemplars of each of the three moments, and of models of the decolonisation of human rights, including that of re-writing their history.
No evidence of mirror self-recognition in keas and Goffin’s cockatoos
Authors: van Buuren M. , Auersperg A. , Gajdon G. , Tebbich S. , von Bayern A. 
Published: September 2018

Abstract
So far only one bird species, a corvid, passed the mark test for mirror self-recognition (MSR) although the results have been questioned. We examined the capacity for MSR in another large-brained avian taxon, parrots, with keas (Nestor notabilis) and Goffin’s cockatoos (Cacatua goffini). After several weeks of mirror habituation, they were subjected to the mark test using different marks and mark placements while facing horizontal and vertical mirrors simultaneously. The keas had an additional control condition in which their reaction towards a marked or non-marked conspecific behind a transparent partition was compared to their own reflection. No evidence of MSR was found in either species. Keas responded to their reflection comparably to a conspecific behind a clear separation. Goffin’s cockatoos showed fewer social responses towards their horizontal reflection compared to their vertical reflection, suggesting that they may interpret them differently.
Globalising the History of Capital: Ways Forward
Authors: Banaji Jairus 
Published: September 2018

AbstractAnievas and Nişancıoğlu’s attempt to shift the terms of the debate about early modern capitalism by a major widening of its perspectives is a welcome move. Accepting this, the paper suggests that their argument can be more forcefully made if the theoretical residues of earlier traditions of Marxist historical explanation are purged from the way they expound that argument. The most ambivalent of these relates to their continued use of the idea of a ‘coexistence of modes of production’. This permeates the confused way they present Atlantic slavery. A second, comparable source of confusion concerns their description of the relationship between merchant capital and the absolutist state. The alliance between the modern state and mercantile capital is radically misrecognised thanks to an uncritical espousal of Anderson’s view of absolutism. The paper suggests that Anievas and Nişancıoğlu might have written a stronger book had they reconceptualised the economic history of capitalism by allowing for a whole epoch dominated by powerful groups of merchant capitalists. In conclusion, I argue (paceMarx) that the commercial capital of the later middle ages/early modern period was the first form in which production began to be subordinated to capital.
Against Hybridism: Why We Need to Distinguish between Nature and Society, Now More than Ever
Authors: Malm Andreas 
Published: September 2018

AbstractIt is fashionable to argue that nature and society are obsolete categories. The two, we are told, can no longer be distinguished from one another; continuing loyalty to the ‘binary’ of the natural and the social blinds us to the logic of current ecological crises. This article outlines an argument for the opposite position: now more than ever – particularly in our rapidly warming world – we need to sift out the social components from the natural, if we wish to understand the crises and retain the possibility of intervening in them. Tracing the current of hybridism to the writings of Bruno Latour, this article ends with a critique of the foremost proponent of a hybridism in Marxist garb: Jason W. Moore. Against his theories, it suggests that historical materialism is a form of property dualism that distinguishes between social and natural relations while considering them equally material in substance. That is also the analytical premise of ecological class hatred, the flames of which ecological Marxism seeks to fan.
Two new species of Sochinsogonia (Hemiptera: Cicadellidae: Cicadellinae) from Philippines
Authors: FENG LING , DIETRICH CHRISTOPHER H. , ZHANG YALIN 
Published: September 2018

Two new species, Sochinsogonia multimacula and S. radicalia spp. nov., of the genus Sochinsogonia Young from Philippines are described and illustrated. A key to distinguish this genus from closely related Oriental genera is provided. A species checklist of the genus is also provided.
Unique fractional calculus engineering laboratory for learning and research
Authors: Khubalkar Swapnil , Junghare Anjali , Aware Mohan , Das Shantanu 
Published: September 2018

In this paper, a novel prototype laboratory is presented for engineering education, in which experiments are based on the fractional calculus. The prototypes of analog and digital fractional-order proportional-integral-derivative (PID) controllers are built in the laboratory. These fractional-order PID controllers are applied to linear and nonlinear plants to demonstrate the effectiveness of fractional-order calculus in real time. These experiments are designed, developed, and implemented on the analog and digital platforms. These controllers are integrated to control the DC motor, brushless DC motor, and magnetic levitation modules through hardware-in-loop as well as stand-alone systems. The analog type of fractional-order PID implementation is carried out by using passive components (i.e. resistances and capacitances) with an operational amplifier. However, real-time digital implementation is carried out using field-programmable gate array and digital signal processor. This paper describes how the experiments on fractional calculus can be tailored for graduate, undergraduate students’ education and extended for research in this emerging area.
Identifying Persistent Postconcussion Symptom Risk in a Pediatric Sports Medicine Clinic
Authors: Howell David R. , Zemek Roger , Brilliant Anna N. , Mannix Rebekah C. , Master Christina L. , Meehan William P. 
Published: September 2018

Background: Although most children report symptom resolution within a month of a concussion, some patients experience persistent postconcussion symptoms (PPCS) that continues for more than 1 month. Identifying patients at risk for PPCS soon after an injury can provide useful clinical information. Purpose: To determine if the Predicting Persistent Post-concussive Problems in Pediatrics (5P) clinical risk score, an emergency department (ED)–derived and validated tool, is associated with developing PPCS when obtained in a primary care sports concussion setting. Study Design: Cohort study; Level of evidence, 3. Methods: We conducted a study of patients seen at a pediatric sports medicine concussion clinic between May 1, 2013, and October 1, 2017, who were <19 years of age and evaluated within 10 days of a concussion. The main outcome was PPCS, defined as symptoms lasting >28 days. Nine variables were used to calculate the 5P clinical risk score, and we assessed the association between the 5P clinical risk score and PPCS occurrence. The secondary outcome was total symptom duration. Results: We examined data from 230 children (mean age, 14.8 ± 2.5 years; 50% female; mean time from injury to clinical assessment, 5.6 ± 2.7 days). In univariable analyses, a greater proportion of those who developed PPCS reported feeling slowed down (72% vs 44%, respectively; P < .001), headache (94% vs 72%, respectively; P < .001), sensitivity to noise (71% vs 43%, respectively; P < .001), and fatigue (82% vs 51%, respectively; P < .001) and committed ≥4 errors in tandem stance (33% vs 7%, respectively; P < .001) than those who did not. Higher 5P clinical risk scores were associated with increased odds of developing PPCS (adjusted odds ratio [OR], 1.62 [95% CI, 1.30-2.02]) and longer symptom resolution times (β = 8.40 [95% CI, 3.25-13.50]). Among the individual participants who received a high 5P clinical risk score (9-12), the majority (82%) went on to experience PPCS. The area under the curve for the 5P clinical risk score was 0.75 (95% CI, 0.66-0.84). After adjusting for the effect of covariates, fatigue (adjusted OR, 2.93) and ≥4 errors in tandem stance (adjusted OR, 7.40) were independently associated with PPCS. Conclusion: Our findings extend the potential use for an ED-derived clinical risk score for predicting the PPCS risk into the sports concussion clinic setting. While not all 9 predictor variables of the 5P clinical risk score were independently associated with the PPCS risk in univariable or multivariable analyses, the combination of factors used to calculate the 5P clinical risk score was significantly associated with the odds of developing PPCS. Thus, obtaining clinically pragmatic risk scores soon after a concussion may be useful for early treatments or interventions to mitigate the PPCS risk.
The Question of Profits
Authors: Hahnel Robin 
Published: September 2018

Where do profits come from? Are they morally justified? Sraffians provide a clear answer to the first question but have declined to give a direct answer to the second question. This article argues that the “fundamental Sraffian theorem” implies a compelling moral critique of profits, but that this critique can be strengthened by replacing the “contribution-based” approach common among economists with a “sacrifice-based” theory consistent with work by modern egalitarian philosophers. JEL Classification: B51, D33, D63
Long-term clinical spectrum and circulating RAS evaluation of anephric patients undergoing hemodialysis: A report of four cases and literature review
Authors: Liu Lin , Zhang Yumei , Fu Fangting , Zhuo Li , Wang Yamei , Li Wenge 
Published: September 2018

Introduction: Bilateral nephrectomy leads to a short-term reduction in blood pressure. This is mainly due to a sharp change in the circulating renin-angiotensin system (RAS), but data on the long-term outcomes of their clinical status and further changes in circulating RAS are rare. Materials and methods: We enrolled four Chinese patients who had both of their kidneys removed two (1), six (1) and eight (2) years prior to this study, respectively. Their clinical data were collected retrospectively and circulating RAS was evaluated by radioimmunoassay. Results: Hypotension after surgery occurred in two patients who suffered thrombosis of the arteriovenous fistula, but no life-threatening complications occurred. The average hemoglobin level was 103.3±12.3 g/l. Two patients without hemorrhage received intravenous erythropoietin (EPO) of 4500–8000 iu/week. Extremely low plasma renin activity (PRA) of 0.08±0.03 ng/ml (normal range 0.93–6.56 ng/ml) showed in the patients. Surprisingly, plasma angiotensin II concentration (71.37±8.28 pg/ml) and aldosterone level (0.17±0.02 ng/mlng/ml) were within the normal range. Conclusions: The four anephric individuals did not suffer life-threatening complications while their hypotension gradually subsided and their EPO dosage was relatively low. Although their PRA level was extremely low, they produced normal levels of angiotensin II and aldosterone in plasma, which indicates the kidney-independent mechanism of angiotensin II production likely compensated in the long term.
Effects of Prolonged Use of Mixed Reality Systems in Occupational Settings Discussion Panel
Authors: Garrett Gregory A. , Reid Christopher R. , Jenkins Michael , Talbot Thomas , Doherty Shawn 
Published: September 2018

Augmented or mixed reality devices overlay computer-generated sensory information that alters one’s current view of the real world. Gaming, military, and instructional applications are fairly prevalent, however, industrial applications are still in their infancy despite this dramatic increase in commercial products. Being a novel application to industry, designers of these systems have focused on function; but have only given a cursory look towards user population safety, ergonomic risk hazards, and long-term exposure concerns. How should designers design for human safety use concerns while maintaining system function? Besides form and function what, if any, safety considerations should public consumers and industries contemplate before buying commercial ready off-the-shelf systems? Ultimately, how do we use ergonomics assessments to better design, assess, and demonstrate business case use of mixed reality devices to benefit labor-intensive occupational tasks? The session will start with initial lectures and introductions from the panel, followed by an encouraged panel discussion with the audience led by the moderators. Moderators: Gregory Garrett, chair & Christopher Reid, co-chair
Choices for long-term hypertensive control in patients after first-ever hemorrhagic stroke: a nationwide cohort study
Authors: Liu Chi-Hung , Lin Yu-Sheng , Chi Ching-Chi , Liou Chia-Wei , Lee Jiann-Der , Peng Tsung-I , Lee Tsong-Hai 
Published: September 2018

Background: To compare the long-term clinical outcomes of different antihypertensive drugs in stable patients after acute hemorrhagic stroke (HS). Methods: From January 2001 to December 2013, patients with first-ever primary HS were identified in the National Health Insurance Research Database, Taiwan. Patients with traumatic intracerebral hemorrhage and secondary HS were excluded. Those with first-ever HS were recruited and classified into three groups: (1) angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB); (2) calcium channel blocker (CCB); and (3) other antihypertensive drugs (comparison) groups. Propensity score matching was used to balance the distribution of baseline characteristics, stroke severity, and medications between any two of the three groups. A validation study was performed using the databank of the Stroke Registry in Chang-Gung Healthcare System to reduce the bias. Primary outcomes were recurrent HS, ischemic stroke, any stroke, and all-cause mortality. Results: Compared to the comparison group, the ACEI/ARB group [35.4% versus 39.3%; hazard ratio (HR), 0.84; 95% confidence interval (CI), 0.74–0.95] and CCB group (33.0% versus 41.9%; HR, 0.72; 95% CI, 0.64–0.81) had a lower risk of all-cause mortality during long-term follow up. The CCB group had a similar risk of all-cause mortality to the ACEI/ARB group. Risks of recurrent HS, ischemic stroke, or any stroke were not different between the study groups. Conclusions: Antihypertensive drug class could be important to long-term outcomes in HS patients in addition to the target control of blood pressure. Both ACEIs/ARBs and CCBs are associated with lower risks of all-cause mortality. Our results may be applied to inform future research on hypertensive control in HS patients.