bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting Mitochondrial Proline Dehydrogenase with a Suicide Inhibitor to Exploit Synthetic Lethal Interactions with p53 Upregulation and Glutaminase Inhibition
Authors: Scott Gary K. , Yau Christina , Becker Beatrice C. , Khateeb Sana , Mahoney Sophia , Jensen Martin Borch , Hann Byron , Cowen Bryan J. , Pegan Scott D. , Benz Christopher C. 
Published: June 2019

Abstract
Proline dehydrogenase (PRODH) is a p53-inducible inner mitochondrial membrane flavoprotein linked to electron transport for anaplerotic glutamate and ATP production, most critical for cancer cell survival under microenvironmental stress conditions. Proposing that PRODH is a unique mitochondrial cancer target, we structurally model and compare its cancer cell activity and consequences upon exposure to either a reversible (S-5-oxo: S-5-oxo-2-tetrahydrofurancarboxylic acid) or irreversible (N-PPG: N-propargylglycine) PRODH inhibitor. Unlike 5-oxo, the suicide inhibitor N-PPG induces early and selective decay of PRODH protein without triggering mitochondrial destruction, consistent with N-PPG activation of the mitochondrial unfolded protein response. Fly and breast tumor (MCF7)-xenografted mouse studies indicate that N-PPG doses sufficient to phenocopy PRODH knockout and induce its decay can be safely and effectively administered in vivo. Among breast cancer cell lines and tumor samples, PRODH mRNA expression is subtype dependent and inversely correlated with glutaminase (GLS1) expression; combining inhibitors of PRODH (S-5-oxo and N-PPG) and GLS1 (CB-839) produces additive if not synergistic loss of cancer cell (ZR-75-1, MCF7, DU4475, and BT474) growth and viability. Although PRODH knockdown alone can induce cancer cell apoptosis, the anticancer potential of either reversible or irreversible PRODH inhibitors is strongly enhanced when p53 is simultaneously upregulated by an MDM2 antagonist (MI-63 and nutlin-3). However, maximum anticancer synergy is observed in vitro when the PRODH suicide inhibitor, N-PPG, is combined with both GLS1-inhibiting and a p53-upregulating MDM2 antagonist. These findings provide preclinical rationale for the development of N-PPG–like PRODH inhibitors as cancer therapeutics to exploit synthetic lethal interactions with p53 upregulation and GLS1 inhibition.
Worlds of Advice
Authors: Siddique Soofia 
Published: June 2019

Abstract
This article situates the nineteenth-century Urdu writer Nazir Ahmad’s Chand Pand as a piece of advice literature on an Arabic-Persian continuum, and equally a text of its time and place. Linguistic features of its discourse show that, as a self-conscious performance of the possibilities of Urdu, it imparts culturally resonant ways of inhabiting a multifarious world, and inscribes an expansive and inclusive view of culture. In particular, the narrative organization of the focal section “A Brief Account of the World” is strongly evocative of a conceptual organization of the world by concentric circles that is comparable to the view of human sociality invoked by the tenth-eleventh century Persian ethicist Miskawayh and illuminates the location of Nazir Ahmad’s text in the continuum of ethics (akhlaq) literature. At the same time, beside these signs of literary cosmopolitanism, I argue that Nazir Ahmad’s account of the world stakes a claim for the irreducible particularity of places and their associated textures of life, and offers a view of the world that supports “place-based thinking or imagination” (Dirlik) as opposed to the potentially obfuscating abstraction of globalized “space.”
On Islands and Deserts
Authors: Leperlier Tristan 
Published: June 2019

Abstract
This article argues for the necessity for world literature and postcolonial studies to examine both global hierarchies of literary legitimacy and those local practices which might challenge them, and give perspectives for other significant geographies. To do so, it focuses on the bilingual and transnational Algerian literary field; this requires different levels of interconnected analysis, namely of the two linguistic subfields, the intermediary level of national literary field and the two Francophone and Arabophone transnational literary fields. Trajectories and literary works of three very different yet linked writers, Rachid Boudjedra, Tahar Djaout and Tahar Ouettar, are examined in turn. The article traces both the global and linguistic inequalities to which they were subjected as well as their practices in order to argue that they reveal unexpected vectors of circulation between spaces and languages. Finally, this piece explores how and why each writer reinvents a world within their desert novels, that is, by narrating wanderings in the desert that are also explorations of national identity.
A re-evaluated taxon: Genetic values and morphological characters support the recognition of the Canary Island juniper of the phoenicea group at a specific level
Authors: ROMO ANGEL , MAZUR MAŁGORZATA , SALVÀ-CATARINEU MONTSERRAT , BORATYŃSKI ADAM 
Published: June 2019

Analyses based on cone, seed and needle characteristics revealed that J. canariensis Guyot in Mathou & Guyot is distinct from both the Circum-Mediterranean J. turbinata and West-Mediterranean J. phoenicea. The genetic differences between these three taxa, which make up the aggregate of J. phoenicea, are found also at a high level. These data support the recognition of the Canarian juniper at the specific level. A key is proposed, in which taxa of the J. phoenicea aggregate can be distinguished on the basis of morphological traits. The nomenclatural name: Juniperus phoenicea subsp. canariensis, widely employed in the literature, is validly published. Besides we adduce that Juniperus canariensis Knight ex Godron, is not a validly published name, and therefore can not be considered an earlier homonym of J. canariensis Guyot in Mathou & Guyot.
Diagnosing Moisture Sources for Flash Floods in the United States. Part II: Terrestrial and Oceanic Sources of Moisture
Authors: Erlingis Jessica M. , Gourley Jonathan J. , Basara Jeffrey B. 
Published: June 2019

Abstract
Backward trajectories were derived from North American Regional Reanalysis data for 19 253 flash flood reports published by the National Weather Service to determine the along-path contribution of the land surface to the moisture budget for flash flood events in the conterminous United States. The impact of land surface interactions was evaluated seasonally and for six regions: the West Coast, Arizona, the Front Range, Flash Flood Alley, the Missouri Valley, and the Appalachians. Parcels were released from locations that were impacted by flash floods and traced backward in time for 120 h. The boundary layer height was used to determine whether moisture increases occurred within the boundary layer or above it. Moisture increases occurring within the boundary layer were attributed to evapotranspiration from the land surface, and surface properties were recorded from an offline run of the Noah land surface model. In general, moisture increases attributed to the land surface were associated with anomalously high surface latent heat fluxes and anomalously low sensible heat fluxes (resulting in a positive anomaly of evaporative fraction) as well as positive anomalies in top-layer soil moisture. Over the ocean, uptakes were associated with positive anomalies in sea surface temperatures, the magnitude of which varies both regionally and seasonally. Major oceanic surface-based source regions of moisture for flash floods in the United States include the Gulf of Mexico and the Gulf of California, while boundary layer moisture increases in the southern plains are attributable in part to interactions between the land surface and the atmosphere.
Impact of Assimilating Upper-Level Dropsonde Observations Collected during the TCI Field Campaign on the Prediction of Intensity and Structure of Hurricane Patricia (2015)
Authors: Feng Jie , Wang Xuguang 
Published: June 2019

Abstract
The dropsondes released during the Tropical Cyclone Intensity (TCI) field campaign provide high-resolution kinematic and thermodynamic measurements of tropical cyclones within the upper-level outflow and inner core. This study investigates the impact of these upper-level TCI dropsondes on analyses and prediction of Hurricane Patricia (2015) during its rapid intensification (RI) phase using an ensemble–variational data assimilation system. In the baseline experiment (BASE), both kinematic and thermodynamic observations of TCI dropsondes at all levels except the upper levels are assimilated. The upper-level wind and thermodynamic observations are assimilated in additional experiments to investigate their respective impacts. Compared to BASE, assimilating TCI upper-level wind observations improves the accuracy of outflow analyses verified against independent atmospheric motion vector (AMV) observations. It also strengthens the tangential and radial wind near the upper-level eyewall. The inertial stability within the upper-level eyewall is enhanced, and the maximum outflow is more aligned toward the inner core. Additionally, the analyses including the upper-level thermodynamic observations produce a warmer and drier core at high levels. Assimilating both upper-level kinematic and thermodynamic observations also improves the RI forecast. Compared to BASE, assimilating the upper-level wind induces more upright and inward-located eyewall convection, resulting in more latent heat release closer to the warm core. This process leads to stronger inner-core warming. Additionally, the initial warmer upper-level inner core produced by assimilating TCI thermodynamic observations also intensifies the convection and latent heat release within the eyewall, thus further contributing to the improved intensity forecasts.
Spectral Empirical Orthogonal Function Analysis of Weather and Climate Data
Authors: Schmidt Oliver T. , Mengaldo Gianmarco , Balsamo Gianpaolo , Wedi Nils P. 
Published: June 2019

Abstract
We apply spectral empirical orthogonal function (SEOF) analysis to educe climate patterns as dominant spatiotemporal modes of variability from reanalysis data. SEOF is a frequency-domain variant of standard empirical orthogonal function (EOF) analysis, and computes modes that represent the statistically most relevant and persistent patterns from an eigendecomposition of the estimated cross-spectral density matrix (CSD). The spectral estimation step distinguishes the approach from other frequency-domain EOF methods based on a single realization of the Fourier transform, and results in a number of desirable mathematical properties: at each frequency, SEOF yields a set of orthogonal modes that are optimally ranked in terms of variance in the L2 sense, and that are coherent in both space and time by construction. We discuss the differences between SEOF and other competing approaches, as well as its relation to dynamical modes of stochastically forced, nonnormal linear dynamical systems. The method is applied to ERA-Interim and ERA-20C reanalysis data, demonstrating its ability to identify a number of well-known spatiotemporal coherent meteorological patterns and teleconnections, including the Madden–Julian oscillation (MJO), the quasi-biennial oscillation (QBO), and the El Niño–Southern Oscillation (ENSO) (i.e., a range of phenomena reoccurring with average periods ranging from months to many years). In addition to two-dimensional univariate analyses of surface data, we give examples of multivariate and three-dimensional meteorological patterns that illustrate how this technique can systematically identify coherent structures from different sets of data. The MATLAB code used to compute the results presented in this study, including the download scripts for the reanalysis data, is freely available online.
What socio-economic factors determine place of death for people with life-limiting illness? A systematic review and appraisal of methodological rigour
Authors: Neergaard Mette Asbjoern , Brunoe Anne Hostrup , Skorstengaard Marianne Hjorth , Nielsen Mette Kjaergaard 
Published: June 2019

Background: Socio-economic factors play important roles in place of death. However, up-to-date knowledge on socio-economic determinants for place of death is warranted including analysis of collinearity between socio-economic determinants. Aim: To examine associations between socio-economic determinants (social class, deprivation level in area of residence, income, education, occupation, urbanisation) and place of death among adult patients with life-limiting illnesses. Furthermore, to describe how these factors are operationalised and examined for collinearity. Design: A systematic review was performed (PROSPERO, record: CRD42018091218) and quality was assessed using the Newcastle–Ottawa Scale. Data sources: A comprehensive search of PubMed, Embase, CINAHL, Scopus and PsycINFO was conducted for studies published from 1 January 2008 until the date of the search (23 March 2018) in English or Scandinavian languages. Results: Of the 1599 unique citations identified, 34 studies were eligible. Dying at home was to a high degree associated with better financial situation and living in rural areas. Furthermore, hospital death was associated with a high level of deprivation in the area of residence and being employed. Regarding educational level, we found mixed and inconclusive results. Conclusion: Inequalities concerning place of death were found, and attention towards socio-economic inequality concerning place of death is necessary, especially in patients with a poor financial status, patients living in deprived and metropolitan areas and patients who are employed. Furthermore, we found a low degree of assessment for collinearity and adjustment of socio-economic variables. These issues should be considered in planning of future studies of socio-economic determinants for place of death.
Accurate prognostic awareness and preference states influence the concordance between terminally ill cancer patients’ states of preferred and received life-sustaining treatments in the last 6 months of life
Authors: Wen Fur-Hsing , Chen Jen-Shi , Chang Wen-Cheng , Chou Wen-Chi , Hsieh Chia-Hsun , Tang Siew Tzuh 
Published: June 2019

Background: Factors facilitating/hindering concordance between preferred and received life-sustaining treatments may be distorted if preferences and predictors are measured long before death. Aim: To examine factors facilitating/hindering concordance between cancer patients’ preferred and received life-sustaining-treatment states in their last 6 months. Design: Longitudinal, observational design. Setting/participants: States of preferred and received life-sustaining treatments (cardio-pulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, and nasogastric tube feeding) were examined in 218 Taiwanese cancer patients by a latent transition model with hidden Markov modeling. Multivariate logistic regression modeling was used to examine factors facilitating/hindering concordance between preferred and received life-sustaining-treatment states. Results: Concordance between preferred and received life-sustaining-treatment states was poor (40.8%, kappa value (95% confidence interval): 0.05 [–0.03, 0.14]). Patients who accurately understood their prognosis and preferred comfort care were significantly more likely to receive preferred life-sustaining treatments before death than those who did not know their prognosis but wanted to know, those who were uniformly uncertain about what life-sustaining treatments they preferred to receive, and those who preferred nutritional support but declined other life-sustaining treatments. Patient age, physician–patient end-of-life-care discussions, symptom distress, and functional dependence were not associated with concordance between preferred and received life-sustaining-treatment states. Conclusion: Prognostic awareness and preferred states of life-sustaining treatments were significantly associated with concordance between preferred and received life-sustaining-treatment states. Personalized interventions should be developed to cultivate terminally ill cancer patients’ accurate prognostic awareness, allowing them to formulate realistic life-sustaining-treatment preferences and facilitating their receiving value-concordant end-of-life care.
Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)
Authors: Liu Changjin , Wen Jing , Xiang Jialin , Ouyang Xuhong , Yang Yan , Lu Wei , Wang Jianwei , Huang Jian , Min Xun 
Published: June 2019

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.
Barriers to ethical decision-making for pre-hospital care professionals
Authors: Torabi Mohammad , Borhani Fariba , Abbaszadeh Abbas , Atashzadeh-Shoorideh Foroozan 
Published: June 2019

Background: Emergency care providers are frequently faces with situations in which they have to make decisions quickly in stressful situations. They face barriers to ethical decision-making and recognizing and finding solutions to these barriers helps them to make ethical decision. Objectives: The purpose of this study was to identify barriers of ethical decision-making in Iranian Emergency Medical Service personnel. Methods: In this qualitative research, the participants (n = 15) were selected using the purposive sampling method, and the data were collected by deep and semi-structured interviews. Finally, the data are analyzed using the content analysis approach. Ethical considerations: Permission to conduct the study was obtained from the Ethics Committee of the Shahid Beheshti University of Medical Sciences. The objectives of the study were explained to the participants and written consent was received from them. Also, participants were assured that necessary measures were taken to protect their anonymity and confidentiality. Findings: The results of the analysis are classified in five main categories. It encompasses the following areas: perception of situation, patient-related factors, input and output imbalance, uncoordinated health system, and paradoxes. Conclusion: Emergency Medical Service personnel make ethical decisions every day. It is important that prehospital personnel know how to manage those decisions properly so that clients’ moral rights are respected. Hence, by identifying the dimensions and obstacles of ethical decision-making in Emergency Medical Service personnel, it is possible to enhance the moral judgment and ethical accountability of the personnel and develop the strategies necessary for ethical decision-making in them.
Myocardial bridge: an unrecognized cause of chest pain in pulmonary arterial hypertension
Authors: Rajmohan Divya , Sung Yon K. , Kudelko Kristina , Perez Vinicio de Jesus , Haddad Francois , Tremmel Jennifer A. , Schnittger Ingela , Zamanian Roham T. , Spiekerkoetter Edda 
Published: June 2019

Pulmonary arterial hypertension (PAH) is characterized by an increased pulmonary vascular resistance resulting in progressive right ventricular hypertrophy and failure. While dyspnea on exertion is the leading symptom at diagnosis, the occurrence of chest pain, although less frequently observed, is an alarming symptom that requires immediate diagnostic work‐up.Here we report the case of a 44‐year‐old woman with severe end‐stage group 1 PAH who had repetitive occurrences of chest pain that led to frequent emergency room visits with documented signs of myocardial ischemia on EKG and troponin leaks. A computed tomography (CT) angiogram of the coronary arteries revealed the presence of a myocardial bridge (MB). An invasive coronary angiogram confirmed a MB over the left anterior descending (LAD) artery compressing the lumen of the LAD. As the patient was deteriorating on maximal medical PAH therapy, she was listed for, and subsequently received, a bilateral lung transplantation. Recognizing that the MB would pose a significant risk for ischemia during surgery as well as continuing source for chest pain after lung transplantation, the MB was surgically “unroofed” during the transplant surgery. The patient did well after surgery and did not complain of any residual chest pain.In conclusion, a MB compressing a segment of the coronary artery could be an under‐diagnosed, but potentially not so rare cause of recurrent chest pain in PAH patients, which requires specialized diagnostic evaluation and treatment
Quality-adjusted life year weights and treatment bias: Theory and evidence from cognitive interviews
Authors: Patenaude Bryan N , Bärnighausen Till 
Published: June 2019

Objectives: The purpose of this research is to understand the thought processes that underpin responses to stated preference approaches for eliciting quality of life, in particular the standard gamble. Methods: We utilize standard gamble preference elicitation survey techniques to elicit quality-adjusted life year weights for two reduced health states: chronic severe depression and total blindness. After the survey, we conduct open-ended qualitative interviews with respondents to determine their thought processes while taking the surveys and to shed light on what their quality-adjusted life year weight is capturing. Survey responses were coded and analyzed for themes in NVivo, the results of which were then formalized in the terminology of decision sciences. Results: The qualitative results of the cognitive interviews present systematic evidence for a type of cognitive bias present in standard gamble quality-adjusted life year weight elicitation, which has not been previously highlighted and which we call treatment bias. We define this treatment bias as the consideration of salient treatment alternatives correlated with a reduced health state, when these alternatives are not explicitly posed in the question. Our formalization of this cognitive behavior demonstrates that treatment bias will always bias the elicited health state utility of treating the illness in question downward. Conclusion: The treatment bias highlighted in this study has implications for economic evaluation when comparing treatment for illnesses where alternative treatments are widely publicized versus those that are not. For example, comparing the effectiveness of treating depression versus arthritis may be biased against depression if advertisements for anti-depressants are more widely viewed by survey respondents than advertisements for arthritis treatments. We propose a statement to be imbedded in all questionnaires regarding stated preference elicitation of quality-adjusted life year weights in order to correct for this bias in future stated preference surveys.