bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Metabolomics Reveals Dysregulation and Diagnostic Potential of Oxylipins in Tumor-induced Osteomalacia
Authors: Gong Yiyi , Ni Xiaolin , Jin Chenxi , Li Xiang , Wang Yujie , Wang Ou , Li Mei , Xing Xiaoping , Wu Zhihong , Jiang Yan , Xia Weibo 
Published: December 2021

Abstract

Context
Excessive production of fibroblast growth factor 23 (FGF23) by a tumor is considered the main pathogenesis in tumor-induced osteomalacia (TIO). Despite its importance to comprehensive understanding of pathogenesis and diagnosis, the regulation of systemic metabolism in TIO remains unclear.

Objective
We aimed to systematically characterize the metabolome alteration associated with TIO.

Methods
By means of liquid chromatography–tandem mass spectrometry–based metabolomics, we analyzed the metabolic profile from 96 serum samples (32 from TIO patients at initial diagnosis, pairwise samples after tumor resection, and 32 matched healthy control (HC) subjects). In order to screen and evaluate potential biomarkers, statistical analyses, pathway enrichment and receiver operating characteristic (ROC) were performed.

Results
Metabolomic profiling revealed distinct alterations between TIO and HC cohorts. Differential metabolites were screened and conducted to functional clustering and annotation. A significantly enriched pathway was found involving arachidonic acid metabolism. A combination of 5 oxylipins, 4-HDoHE, leukotriene B4, 5-HETE, 17-HETE, and 9,10,13-TriHOME, demonstrated a high sensitivity and specificity panel for TIO prediction screened by random forest algorithm (AUC = 0.951; 95% CI, 0.827-1). Supported vector machine modeling and partial least squares modeling were conducted to validate the predictive capabilities of the diagnostic panel.

Conclusion
Metabolite profiling of TIO showed significant alterations compared with HC. A high-sensitivity and high-specificity panel with 5 oxylipins was tested as diagnostic predictor. For the first time, we provide the global profile of metabolomes and identify potential diagnostic biomarkers of TIO. The present work may offer novel insights into the pathogenesis of TIO.
Progression of Vertebral Fractures in Patients with Adrenocortical Carcinoma Undergoing Mitotane Therapy
Authors: Cosentini Deborah , Grisanti Salvatore , Hadoux Julien , Libè Rossella , Frigerio Michele , Laganà Marta , Deschamps Frederic , Zamparini Manuel , Lamartina Livia , Pedersini Rebecca , Valsecchi Clara , Maroldi Roberto , Al Ghuzlan Abir , Terzolo Massimo , Gasparotti Roberto , Baudin Eric , Berruti Alfredo 
Published: December 2021

Abstract

Context
Patients with adrenocortical carcinoma (ACC) are frequently on mitotane therapy for a long time period. The drug exerts adrenolytic activity requiring glucocorticoid supplementation, which can be potentially detrimental for bone.

Objective
To explore whether mitotane with/without chemotherapy is associated with an increased proportion of morphometric vertebral fractures (VFs) in ACC patients. Secondary objectives were proportion of patients with VF progression, or worsening of the spinal deformity index (SDI) during mitotane therapy; and to explore predictive factors of VF progression and a prognostic role of VF progression.

Methods
Multicenter, retrospective cohort study of patients with ACC who received mitotane alone or in association to chemotherapy, recruited from January 2010 to January 2020 in 2 reference centers in Italy and France.

Results
A significant increase in the frequency of VFs before and after mitotane therapy was seen both in Italian (28.3% vs 47.8%, P = .04) and French (17.8% vs 35.6%, P = .04) series. VF progression was observed in 39.1%, and 28.9% of patients, respectively. Baseline VFs and increased patient body mass index, but not the dose of cortisol supplementation, showed an independent association with VF progression at multivariate analysis. Among the 72 advanced ACC patients, progression of VFs was associated with a poorer survival.

Conclusion
The administration of mitotane with/without chemotherapy in ACC patients impairs bone health independently from cortisol supplementation. Appropriate preventive measures to decrease the fracture risk should be implemented in these patients.
Multiple Perspectives on Recent Trends in Unwanted Fertility in Low- and Middle-Income Countries
Authors: Casterline John B. , El-Zeini Laila O. 
Published: December 2021

Abstract
The last four decades have witnessed large declines in fertility globally. This study uses data from 78 low- and middle-income countries to examine concurrent trends in unwanted fertility. Three measures of unwanted fertility are contrasted: the conventional unwanted total fertility rate, a proposed conditional unwanted fertility rate, and the percentage of births unwanted. Incidence of unwanted births and prevalence of exposure to unwanted births are both derived from answers to questions on prospective fertility preference, recognized as the most valid and reliable survey measure of preferences. Country-level trends are modeled both historically and with the decline in total fertility, with a focus on regional differentials. Results show that unwanted fertility rates—especially the conditional unwanted fertility rate—have declined substantially in recent decades. By contrast, the percentage of births unwanted has declined less, remaining stable or even increasing: from a birth cohort perspective, declines in unwanted fertility have been far more modest than the increased parental success in avoiding unwanted births. The regional patterns suggest that sub-Saharan Africa has several similarities with other major regions but also some peculiar features, including a recent stall in the decline of unwanted fertility that persists after controlling for the stage of fertility transition.
A mapping of health education institutions and programs in the WHO African Region
Authors: Yarmoshuk Aaron N. , Abomo Pierre , Fitzgerald Niamh , Cole Donald C. , Fontanet Arnaud , Adeola Henry A. , Zarowsky Christina , Pulford Justin 
Published: December 2021

Background: Information on health education institutions is required for planning, implementing and monitoring human resources for health strategies. Details on the number, type and distribution of medical and health science programs offered by African higher education institutions remains scattered. Methods: We merged and updated datasets of health professional and post-graduate programs to develop a mapping of health education institutions covering the World Health Organization African Region as of 2021. Results: Nine hundred and nine (909) institutions were identified in the 47 countries. Together they offered 1,157 health professional programs (235 medicine, 718 nursing, 77 public health and 146 pharmacy) and 1,674 post-graduate programs (42 certificates, 1,152 Master’s and 480 PhDs). Regionally, East Africa had the most countries with multiple academic health science centres - institutions offering medical degrees and at least one other health professional program. Among countries, South Africa had the most institutions and post-graduate programs with 182 and 596, respectfully. A further five countries had between 53-105 institutions, 12 countries had between 10 and 37 institutions, and 28 countries had between one and eight institutions. One country had no institution. Countries with the largest populations and gross domestic products had significantly more health education institutions and produced more scientific research (ANOVA testing). Discussion: We envision an online database being made available in a visually attractive, user-friendly, open access format that nationally, registered institutions can add to and update. This would serve the needs of trainees, administrators, planners and researchers alike and support the World Health Organization’s Global strategy on human resources for health: workforce 2030.
Modified Kibria-Lukman (MKL) estimator for the Poisson Regression Model: application and simulation
Authors: Aladeitan Benedicta B. , Adebimpe Olukayode , Lukman Adewale F. , Oludoun Olajumoke , Abiodun Oluwakemi E. 
Published: December 2021

Background: Multicollinearity greatly affects the Maximum Likelihood Estimator (MLE) efficiency in both the linear regression model and the generalized linear model. Alternative estimators to the MLE include the ridge estimator, the Liu estimator and the Kibria-Lukman (KL) estimator, though literature shows that the KL estimator is preferred. Therefore, this study sought to modify the KL estimator to mitigate the Poisson Regression Model with multicollinearity. Methods: A simulation study and a real-life study was carried out and the performance of the new estimator was compared with some of the existing estimators. Results: The simulation result showed the new estimator performed more efficiently than the MLE, Poisson Ridge Regression Estimator (PRE), Poisson Liu Estimator (PLE) and the Poisson KL (PKL) estimators. The real-life application also agreed with the simulation result. Conclusions: In general, the new estimator performed more efficiently than the MLE, PRE, PLE and the PKL when multicollinearity was present.
May Mutation of SNP rs1800947 Affects Length of Stay Outcome of COVID-19 suspects?
Authors: Zulmansyah Zulmansyah , Nugraha Gaga Irawan , Agustian Dwi , Gurnida Dida Akhmad 
Published: December 2021

Coronavirus disease 2019 (COVID-19) is a new type of respiratory infection that first emerged in December 2019 in Wuhan, Hubei, China. COVID-19 is caused by a new type of virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aims to determine the association of SNP CRP rs1800947 gene in suspected COVID-19 patients to length of stay at Al Ihsan Hospital, and Banten Hospital in June-November 2020. This study used data from 60 patients, all patients were suspect COVID-19. The subject was 29 COVID-19 people were confirmed, whereas 31 people were not. A statistics analysis due to pearson correlation and linear multi regretion. This study found a significant assosiation between the subject. The results of this study were the relationship between SNP rs1800947 and outcome, a fairly strong association level relationship was found in the SNP rs1800947 (p-value= 0.045, association= 0.537). The association between length of stay and CRP levels has a low level of association (p-value=0.015, association=0.378). The SNP genotype rs1800947 G had a longer treatment duration of 0.14778 days compared to the SNPrs1800947 C genotype. CRP levels showed that higher CRP levels increased the length of treatment compared to normal CRP levels. Where high CRP levels are at risk of 0.6330 days longer than normal CRP while very high CRP is at risk of 2.9561 days longer than Normal CRP levels. In general, the gene SNP rs1800947 and CRP levels, together affect the outcome of patients with suspected COVID-19.
Leveraging capabilities for the creation of a smart, healthy and personalized breakfast: a case study of innovation ecosystems in the EU
Authors: Talens Clara , Rios Yolanda , Santa Cruz Elena 
Published: December 2021

Background: Rapid population growth, increasing urbanization, and an expanding global middle class has profound impacts on food and nutrition. In the long run the smart home appliance industry will reflect the social, technological, and demographic forces around food without losing the authenticity of food traditionally prepared in the kitchen. This paper investigates the capability of an innovation ecosystem to co-create a new consumer-driven breakfast concept. Methods: Three smart cooking technology providers (3D food printing, digital sous-vide cooking and instant dough baking), one ingredient supplier, and a top-tier food research and innovation centre shared resources to carry out common tasks such as market research, product development, and consumer taste tests. Consumers were segmented into four types of households (single, young families, consolidated families, and senior). An online community (40 participants), nine focus groups, two interviews with eight experts, and one quantitative study with 2055 cases were carried out in Spain, UK, and Germany. The findings provided both theoretical and practical insights into the perception of the three smart cooking devices per type of household and per country. A combination of technologies was used to develop the new breakfast concept for the target group and country with the most positive perception. Results: A customized, fresh, tasty, nutritious, and healthy 3D printed breakfast bar was developed for senior consumers in Spain. Sensory analysis and acceptability were tested with 80 senior consumers aged between 45 and 75 years and divided in two groups: 46-60 years (mature), and 61-75 (senior). Around 56% of consumers increased their acceptance of the new breakfast bar after being informed about the technological, nutritional, and convenient benefits of the new breakfast concept. Conclusions: A strategic collaborative innovation method was implemented to show how innovation ecosystems can encourage productive entrepreneurship, and help start-ups define and identify their target customer segments.
A Comparison of Two Mixed-Integer Linear Programs for Piecewise Linear Function Fitting
Authors: Warwicker John Alasdair , Rebennack Steffen 
Published: December 2021

The problem of fitting continuous piecewise linear (PWL) functions to discrete data has applications in pattern recognition and engineering, amongst many other fields. To find an optimal PWL function, the positioning of the breakpoints connecting adjacent linear segments must not be constrained and should be allowed to be placed freely. Although the univariate PWL fitting problem has often been approached from a global optimisation perspective, recently, two mixed-integer linear programming approaches have been presented that solve for optimal PWL functions. In this paper, we compare the two approaches: the first was presented by Rebennack and Krasko [Rebennack S, Krasko V (2020) Piecewise linear function fitting via mixed-integer linear programming. INFORMS J. Comput. 32(2):507–530] and the second by Kong and Maravelias [Kong L, Maravelias CT (2020) On the derivation of continuous piecewise linear approximating functions. INFORMS J. Comput. 32(3):531–546]. Both formulations are similar in that they use binary variables and logical implications modelled by big-[Formula: see text] constructs to ensure the continuity of the PWL function, yet the former model uses fewer binary variables. We present experimental results comparing the time taken to find optimal PWL functions with differing numbers of breakpoints across 10 data sets for three different objective functions. Although neither of the two formulations is superior on all data sets, the presented computational results suggest that the formulation presented by Rebennack and Krasko is faster. This might be explained by the fact that it contains fewer complicating binary variables and sparser constraints. Summary of Contribution: This paper presents a comparison of the mixed-integer linear programming models presented in two recent studies published in the INFORMS Journal on Computing. Because of the similarity of the formulations of the two models, it is not clear which one is preferable. We present a detailed comparison of the two formulations, including a series of comparative experimental results across 10 data sets that appeared across both papers. We hope that our results will allow readers to take an objective view as to which implementation they should use.
Dynamic Pricing and Inventory Control with Fixed Ordering Cost and Incomplete Demand Information
Authors: Chen Boxiao , Simchi-Levi David , Wang Yining , Zhou Yuan 
Published: December 2021

We consider the periodic review dynamic pricing and inventory control problem with fixed ordering cost. Demand is random and price dependent, and unsatisfied demand is backlogged. With complete demand information, the celebrated [Formula: see text] policy is proved to be optimal, where s and S are the reorder point and order-up-to level for ordering strategy, and [Formula: see text], a function of on-hand inventory level, characterizes the pricing strategy. In this paper, we consider incomplete demand information and develop online learning algorithms whose average profit approaches that of the optimal [Formula: see text] with a tight [Formula: see text] regret rate. A number of salient features differentiate our work from the existing online learning researches in the operations management (OM) literature. First, computing the optimal [Formula: see text] policy requires solving a dynamic programming (DP) over multiple periods involving unknown quantities, which is different from the majority of learning problems in OM that only require solving single-period optimization questions. It is hence challenging to establish stability results through DP recursions, which we accomplish by proving uniform convergence of the profit-to-go function. The necessity of analyzing action-dependent state transition over multiple periods resembles the reinforcement learning question, considerably more difficult than existing bandit learning algorithms. Second, the pricing function [Formula: see text] is of infinite dimension, and approaching it is much more challenging than approaching a finite number of parameters as seen in existing researches. The demand-price relationship is estimated based on upper confidence bound, but the confidence interval cannot be explicitly calculated due to the complexity of the DP recursion. Finally, because of the multiperiod nature of [Formula: see text] policies the actual distribution of the randomness in demand plays an important role in determining the optimal pricing strategy [Formula: see text], which is unknown to the learner a priori. In this paper, the demand randomness is approximated by an empirical distribution constructed using dependent samples, and a novel Wasserstein metric-based argument is employed to prove convergence of the empirical distribution. This paper was accepted by J. George Shanthikumar, big data analytics.
A Dimensão Externa dos Regionalismos para Além do Comércio: A Experiência do Mercosul l La Dimensión Externa de los Regionalismos más Allá del Comércio: La Experiencia del Mercosur
Authors: Pessoa Luan Olliveira 
Published: December 2021

Em 2019, a conclusão das negociações comerciais do acordo entre Mercosul e UE, marcante na dimensão externa do Mercosul, foi noticiada como fim do isolamento do mesmo. Se antes estava isolado e, assim, não havia interações com o exterior, então somente negociações e tratados comerciais podem constituir a dimensão externa dos regionalismos e, especificamente, a do Mercosul? Tal indagação remete a temas menos estudados relativamente na literatura especializada em regionalismo. Com tal relevância, a pesquisa apresentada neste artigo revisou criticamente a literatura mirando a indagação, contemplando aspectos teóricos sobre a dimensão externa e apontamentos históricos relativos ao Mercosul. Assim, alcança uma compreensão ampla de que a dimensão externa dos regionalismos pode abranger, considerando identidade regional, difusão institucional, conexão entre o regional e o global, engajamento das regiões com o resto do mundo. E, nessa abrangência, concebe as relações externas do Mercosul como diversas e bem demasiadamente anteriores a 2019.Palavras-chave: Dimensão Externa; Mercosul; Regionalismo.RESUMENEn 2019, la conclusión de las negociaciones comerciales del acuerdo entre Mercosur y la UE, hito en la dimensión externa del Mercosur, se notició como el fin del aislamiento del mismo. Si antes estaba aislado y, así, no había interacción con el exterior, por lo tanto, ¿sólo pueden negociaciones y tratados comerciales constituir la dimensión externa de los regionalismos y, específicamente, la del Mercosur? Tal indagación se refiere a temas menos estudiados relativamente en la literatura especializada en regionalismo. Con tal relevancia, la investigación presentada en este artículo revisó críticamente la literatura mirando la indagación, contemplando aspectos teóricos acerca de la dimensión externa y apuntamientos históricos relativos al Mercosur. Así, logra una comprensión amplia de lo que la dimensión externa de los regionalismos puede abarcar, teniendo en cuenta identidad regional, difusión institucional, conexión entre lo regional y lo global, envolvimiento de las regiones con el resto del mundo. Y, en ese ámbito, concibe las relaciones externas del Mercosur como diversas y demasiado anteriores a 2019.Palabras Clave: Dimensión Externa; Mercosur; Regionalismo. Recebido em: 02/04/2021 | Aceito em: 03/08/2021.
O Período Hegemônico da Década de 1990 e suas Instituições Internacionais: O Caso do Tribunal Penal Internacional l The Hegemonic Period of 1990’s and Its International Institutions: The Case of International Criminal Court
Authors: Felix Hugo 
Published: December 2021

O presente artigo tem como objetivo questionar o enquadramento genérico dado ao Tribunal Penal Internacional como instituição de governança democrática liberal imposta pela hegemonia estadunidense na década de 1990, utilizando os parâmetros conceituais da Teoria Crítica estabelecida por Robert Cox. São levantados três aspectos: os Estados Unidos não aderiram ao Tribunal; a jurisdição do Tribunal foi concebida majoritariamente por países em desenvolvimento; e grande parte de mandados do TPI são expedidos para o continente africano. Para avaliar essa situação, o artigo se dividirá em duas partes. A primeira consiste na apresentação da abordagem teórica e no enquadramento dos Estados Unidos como ator hegemônico do período a partir dos conceitos de Cox. A segunda apresentará uma análise das negociações para a construção do TPI, assim como das relações dos EUA e dos países africanos com o Tribunal. Por fim, chega-se à conclusão de que que o TPI apresenta caráter peculiar e ambíguo na política internacional.Palavras-chave: Teoria Crítica; Hegemonia; Tribunal Penal Internacional.ABSTRACTThis article aims to question the generic framework given to the International Criminal Court as an institution of liberal democratic governance imposed by American hegemony in the 1990s, using the conceptual parameters of the Critical Theory established by Robert Cox. Three aspects are brought to the debate: the United States did not adhere to the Tribunal; the jurisdiction of the Court was conceived mainly by developing countries; and a large number of ICC warrants are sent to the African continent. To assess this situation, the article will be divided in two parts. The first one consists of presenting the theoretical approach and also focused on framing the United States as a hegemonic actor of the period based on Cox's concepts. The second part will present an analysis of the negotiations to the construction of the ICC, as well as the relations of the US and African countries with the Court. Finally, it is concluded that the ICC is in a peculiar situation and ambiguous in international politics.Keywords: Critical Theory; Hegemony; International Criminal Court. Recebido em: 10/04/2021 | Aceito em: 17/08/2021.