bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of medicines consumption in Portugal before and during the financial crisis
Authors: Donato António Augusto , Pita João Rui , Batel-Marques Francisco 
Published: July 2021

Abstract

Background
In May 2011, the Portuguese Government signed a Memorandum of Understanding with the European Commission, the European Central Bank and the International Monetary Fund, including detailed measures to control health costs, allowing Portugal to receive a financial rescue package. This study aims to investigate medicines utilization in the outpatient sector during Troika’s financial rescue.

Methods
Using Defined Daily Dose per million inhabitants per year as a measurement unit, we compared medicines utilization with other relevant indicators over 5-year intervals for a total period of 20 years, based on a built-in inventory of national outpatient drug use using the Intercontinental Medical Statistics Health and Anatomical Therapeutic Chemical index of the World Health Organization databases. The calculation was made on the basis of both compound and year-on-year growth rates.

Results
With the exception of the interval 2009–11, an absolute rise in consumption was observed over the 20-year period. The downturn occurred prior to financial rescue, when expenditure management mechanisms were already in place, and coincided with an increase in out-of-pocket spending. With the decline of cost for patients, the access trend returned to being positive, but at a slower pace.

Conclusion
The rise in out-of-pocket and austerity measures may have led to decreased access to medicines. The findings of this study suggest that this impact was influenced by public cost-saving policies implemented even before the financial rescue. The results show that price reduction attenuated the repercussion of the measures.
Responses of cucumber (Cucumis sativusL.) rhizosphere microbial community to some agronomic management practices
Authors: Ezazi Robab , Ahmadzadeh Masoud , Majidian Sina , Stefani Erika , Pindo Massimo , Donati Claudio 
Published: July 2021

ABSTRACTThe microbial communities associated to the rhizosphere (the rhizomicrobiome) have a substantial impact on plant growth and yield. Understanding the effects of agricultural management on the rhizomicrobiome is very important for selecting efficient practices. By sequencing the V4 region of 16S rRNA for bacteria and the ITS1 regions and fungi, we investigated the influences of agronomic practices, including cucumber grafting on cucurbit hybrid (Cucurbita moschata × C. maxima), cucumber-garlic intercropping, and treatment with fungicide iprodione-carbendazim on cucumber rhizosphere microbial communities during plant growth. Soil dehydrogenase activity (DHA) and plant vegetative parameters were assessed as an indicator of overall soil microbial activity. We found that both treatments and growth stage induced significant shifts in microbial community structure. Grafting had the highest number of differentially abundant OTUs compared to control samples, followed by intercropping and fungicide treatment, while plant development stage affected both alpha and beta diversities indices and composition of the rhizomicrobiome. DHA was more dependent on plant growth stages than on treatments. Among the assessed factors, grafting and plant developmental stage resulted in the greatest changes in the microbial community composition. Grafting also increased the plant growth parameters, suggesting that this method should be further investigated in vegetable production systems.
Fermenting Futures: an artistic view on yeast biotechnology
Authors: Dumitriu Anna , May Alex , Ata Özge , Mattanovich Diethard 
Published: July 2021

ABSTRACT
BioArt is a new discipline where artists employ materials and techniques of modern life sciences and create novel meanings of biology, often involving living organisms such as tissue culture, bacteria and yeasts, which may also be genetically engineered. The authors have engaged in a collaboration to develop ‘Fermenting Futures’, a project designed to explore the significance of yeast for early human history by enabling baking and brewing, all the way to industrial biotechnology and synthetic biology with their potential contributions to fight the climate change. Research in two of the authors’ lab provides the materials and thematic lines for the artists to develop their installations. The two main pieces reflect on fermentation as a metabolic trait of baker's yeast and its enormous transformational power for human society, and on the application of synthetic biology to enable yeast to grow and produce materials from carbon dioxide. The role of BioArt to support public engagement and science dissemination is discussed, highlighting the importance of collaborations of scientists and artists on equal terms, as showcased here.
Pain and Functional Limitations Among Midlife and Older Canadians: The Role of Discrimination, Race, and Sense of Belonging
Authors: Vang Zoua M , Chau Shirley , Kobayashi Karen M , Owen Mary J , McKenzie-Sampson Safyer , Mayrand-Thibert Jeanne , Brass Gregory M 
Published: July 2021

Abstract

Objectives
We drew on fundamental cause theory and the weathering hypothesis to examine how discrimination influences aging for midlife and older adults in Canada.

Methods
Using nationally representative data, we assessed the associations between discrimination and pain and functional limitations among adults aged 45 years and older. Discrimination was measured using a modified version of the Everyday Discrimination Scale. Chi-square tests were performed to check for baseline differences in the dependent and key predictor variables by race. Logistic regression was used to estimate the associations of discrimination, race, and sense of belonging with pain and functional limitations, net of sociodemographic characteristics, and socioeconomic status.

Results
Indigenous respondents showed a clear health disadvantage, with higher rates of pain and functional limitations compared to Whites and Asians. Self-reported discrimination was also higher for Indigenous midlife and older adults than for their White and Asian age counterparts. Discrimination had a direct and robust association with pain (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.31–1.87) and functional limitations (OR 1.55, 95% CI 1.29–1.87). However, race moderated the impact of discrimination on functional limitations for Blacks. Finally, a strong sense of belonging to one’s local community was protective against pain and functional limitations for all racial groups.

Discussion
Future research needs to further examine the impact of discrimination on Indigenous peoples’ aging process. High rates of discrimination coupled with a greater burden of pain mean that Indigenous midlife and older adults may require additional and targeted health and social service resources to age successfully.
The COVID-19 Pandemic: Stress Test for Intellectual Property and Pharmaceutical Laws
Authors: Oser Andreas 
Published: July 2021

Abstract
The COVID-19 pandemic poses a challenge to certain standards in patent law as well as in pharmaceutical law. This paper discusses questions as to whether and under what conditions government-ordered or privately claimed compulsory licensing can contribute to controlling the pandemic. The existing obstacles and conflicts under the current legal framework, such as a lack of international harmonization and a lack of coherence between patent law (compulsory licensing) and pharmaceutical law (data protection), are outlined and discussed. A possible solution could lie in a modernization of relevant legal provisions to create an internationally harmonized balance between the public interest in using important patents in the present and in future emergency situations and the interest of patent owners and data and market exclusivity holders in allowing exemptions within clearly defined limits. The article concludes with a discussion of conditions that may influence possible solutions.
Mobile health apps to reduce sedentary behavior: a scoping review
Authors: Ueno Deisy Terumi , Guerra Paulo Henrique , Christofoletti Ana Elisa Messetti , Bonolo Angélica , Nakamura Priscila Missaki , Kokubun Eduardo 
Published: July 2021

Summary
Given the continued increase in mobile health applications (apps) aimed at healthcare and the recognition of sedentary behavior (SB) as a public health problem, the goal of this scoping review study was to summarize the effects of interventions based on mobile health apps designed to reduce SB in adults, with a specific focus on SB. The electronic databases PubMed, PsycINFO, SportDISCUS, Web of Science, and manual searches in reference lists were conducted on papers published up to September 2020. Nine out of the 897 studies researched were included and composed the descriptive synthesis. The investigations found in the present study showed a decrease in time spent on television viewing and in total time spent sitting, as well as an increase in the number of SB breaks after interventions based on mobile health apps. In conclusion, despite the growing interest in intervention programs in SB, only nine studies have used smartphone apps as a strategy to reduce SB in adults. Mobile health apps were proved to be effective in SB reduction, as assessed by different parameters, and should be encouraged. However, further studies are needed to verify the long-term effects of the utilization of such applications.
Three decades of ASD genetics: building a foundation for neurobiological understanding and treatment
Authors: Eyring Katherine W , Geschwind Daniel H 
Published: July 2021

Abstract
Methodological advances over the last three decades have led to a profound transformation in our understanding of the genetic origins of neuropsychiatric disorders. This is exemplified by the study of autism spectrum disorders (ASDs) for which microarrays, whole exome sequencing and whole genome sequencing have yielded over a hundred causal loci. Genome-wide association studies in ASD have also been fruitful, identifying 5 genome-wide significant loci thus far and demonstrating a substantial role for polygenic inherited risk. Approaches rooted in systems biology and functional genomics have increasingly placed genes implicated by risk variants into biological context. Genetic risk affects a finite group of cell-types and biological processes, converging primarily on early stages of brain development (though, the expression of many risk genes persists through childhood). Coupled with advances in stem cell-based human in vitro model systems, these findings provide a basis for developing mechanistic models of disease pathophysiology.
From colonial to multilateral international law: A global capitalism and law investigation
Authors: Alter Karen J 
Published: July 2021

Abstract
This Foreword integrates international law, international relations, and global history scholarship to understand two global trends that are in tension with each other: (i) the shift from European colonial dominance to a law-based multilateralism, which enabled a more equal and inclusive international law, and (ii) global capitalism which, across time, has been a political and economic force that, left to its own devices, promotes exclusion and inequality. Alter builds an encompassing conception of global economic law to show the interplay of colonial law, private law, domestic law, and international law in enabling and constraining global capitalism across time. The investigation looks backwards so as to think forward. The larger goal of the endeavor is to imagine how an Asian law-based capitalism might continue past trends and recreate continuities despite a professed desire to be different. Just as capitalism once locked in colonial features despite the shift to multilateral international law, multilateralism and capitalism may be forces that sustain the very features of the Western Liberal International Order that China seeks to move beyond.
Crippling Compensation in the International Law Commission and Investor–State Arbitration
Authors: Paparinskis Martins 
Published: July 2021

Abstract
Is there an exception to the principle of full reparation in international investment arbitration for cases in which full compensation is crippling for the responsible State or its peoples? The routine presentation and consideration of billion-dollar-plus investment arbitration claims in the first half of 2021 suggests that this subject has not been invented in order to enable it to be written about but is one of considerable importance for the field of international investment law and its actors. The frame of reference in a discussion about compensation in investment law is provided by the law of State responsibility, strongly shaped by the 2001 International Law Commission’s Articles on Responsibility of States for Internationally Wrongful Acts (2001 ILC Articles on State Responsibility), which treat crippling compensation as permissible as a matter of content of responsibility. The argument for the permissibility of crippling compensation explicitly assumed the rarity of such claims; safeguards in primary, secondary, and tertiary rules for the few cases when they did arise; and the enlightened self-interest of States as repeat-playing actors in not making them—and perhaps implicitly scepticism about compound interest and Discount Cash Flow valuation. None of these assumptions holds true in modern investor State arbitration. Nevertheless, the predominant reaction to crippling compensation claims has been silence by tribunals and respondent States, suggestive in legal terms of endorsement of their permissibility in line with the 2001 ILC Articles on State Responsibility. There is some scope for addressing crippling compensation within the 2001 ILC Articles on State Responsibility, both indirectly (challenging the meaningfulness of the question in the first place or considering crippling compensation as part of the general discussion of the content of responsibility) and directly, under the rubrics of circumstances precluding wrongfulness and enforcement. The case can also be made for moving beyond the 2001 ILC Articles on State Responsibility, by emphasising the difference between implementation of responsibility in inter-State and investor–State legal relations or even directly arguing for a change of the applicable customary rule.
In low-risk patients aged &gt;70–75 with severe aortic stenosis, is transcatheter superior to surgical aortic valve replacement in terms of reported cardiovascular composite outcomes and survival?
Authors: Magro Pedro Lamares , Sousa-Uva Miguel 
Published: July 2021

AbstractA best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: In low-risk patients aged &gt;70–75 with severe aortic stenosis, is transcatheter superior to surgical aortic valve replacement in terms of reported composite outcomes and survival? More than 73 papers were found using the reported search, of which 8 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. The only low-risk randomized control trial to date [Nordic Aortic Valve Intervention (NOTION)] regarding an elderly population did not show a statistically significant difference between the 2 approaches regarding the composite endpoint of death, stroke or myocardial infarction. A subgroup analysis of elderly patients in the 2 main low-risk randomized control trials did not yield statistically different results from those of the overall population; the results indicated the superiority of transcatheter aortic valve implantation regarding the composite of death, stroke or rehospitalization at 1 year [The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis (PARTNER 3)] and non-inferiority regarding a composite of death or stroke at 2 years [Medtronic Evolut Transcatheter Aortic Valve Replacement in Low-Risk Patients (Evolut LR)]. The results from lower evidence studies are largely consistent with these findings. Overall, there is no compelling evidence indicating that older age should be an isolated criterion for the choice between transcatheter aortic valve replacement and surgical aortic valve replacement in otherwise low-risk patients. The superiority of either technique regarding the aforementioned composite short-term outcomes in this particular subgroup of patients is unclear.
Case-Control Study of Household and Environmental Transmission of Typhoid Fever in India
Authors: Giri Sidhartha , Mohan Venkata Raghava , Srinivasan Manikandan , Kumar Nirmal , Kumar Vinoth , Dhanapal Pavithra , Venkatesan Jayalakshmi , Gunasekaran Annai , Abraham Dilip , John Jacob , Kang Gagandeep 
Published: July 2021

Abstract

Background
Typhoid fever causes substantial morbidity and mortality in low- and middle-income countries. We conducted a case-control study in Vellore, southern India, to understand risk factors for transmission of typhoid.

Methods
From April 2018 to October 2019, households of blood culture-confirmed typhoid cases that occurred within a fever surveillance cohort aged 6 months–15 years, and controls matched for age, sex, geographic location, and socioeconomic status, were recruited. Information on risk factors was obtained using standard questionnaires. Household and environmental samples were collected for detection of Salmonella Typhi using real-time polymerase chain reaction. Multivariable analysis was used to evaluate associations between risk factors and typhoid.

Results
One hundred pairs of cases and controls were recruited. On multivariable regression analysis, mothers eating food from street vendors during the previous week (odds ratio [OR] = 2.04; 95% confidence interval [CI], 1.03–4.12; P = .04) was independently associated with typhoid, whereas treatment of household drinking water (OR = 0.45; 95% CI, 0.25–0.80; P = .007) was protective. There was no significant difference in S Typhi detection between the environmental samples from case and control households.

Conclusions
Street-vended food is a risk factor for typhoid in densely populated urban communities of Vellore. Improved sanitation facilities and awareness about point-of-use water treatment are likely to contribute to typhoid control.
Measurement of acetabular wall indices: comparison between CT and plain radiography
Authors: Nazaroff Jaron , Mark Bryan , Learned James , Wang Dean 
Published: July 2021

Abstract
The purpose of this study was to compare measurements of anterior wall index (AWI) and posterior wall index (PWI) on computed tomography (CT) to those on radiographs (XR). A consecutive cohort of 33 patients (45 hips total) being evaluated for hip pain with both XR and CT was examined. Preoperative measurements of AWI and PWI were performed utilizing supine anteroposterior pelvic XR and coronal and swiss axial CT scans by two independent raters. Mean differences between XR and CT measurements were compared, and agreement between measurements was assessed using the concordance correlation coefficient (rc) and Bland–Altman analysis. A total of 39 hips in 28 patients were analyzed. The mean patient age was 31.1 ± 9.0 years, and 50% were female. Mean AWI and PWI on XR was 0.50 ± 0.14 and 0.91 ± 0.12, respectively. Measured values of AWI were consistently larger (0.08 ± 0.10, P &lt; 0.01) on XR compared with both coronal and swiss axial CT, with moderate agreement between XR and CT measurements (rc = 0.68–0.70). Measured values of PWI were consistently smaller (0.15 ± 0.12, P &lt; 0.05) on XR compared with both coronal and swiss axial CT, with poor agreement between XR and CT measurements (rc = 0.37–0.45). Measured values of acetabular wall indices on XR were consistently larger for AWI and smaller for PWI relative to CT. Agreement between XR and CT measures of the indices were moderate to poor. This highlights the need for standardization of XR- and CT-based measurements to improve assessment of acetabular coverage and subsequent clinical decision-making.
The ICC, Self-created Challenges and Missed Opportunities to Legitimize Authority over Non-states Parties
Authors: McIntyre Gabrielle 
Published: July 2021

Abstract
The Prosecutor of the International Criminal Court (ICC) has consistently embroiled the Court in situations involving allegations of the commission of crimes by non-state party nationals on the territory of states parties. For the most part, the Prosecutor has assumed the jurisdiction of the Court over non-state party nationals is well-founded by reference to the provisions of the Rome Statute, without any examination as to why or how those provisions bind non-states parties nationals. Where the Prosecutor has specifically sought a legal ruling from the Chambers on the exercise of jurisdiction over non-state party nationals, the Chambers have failed to address the legal issues in a consistent, persuasive and coherent manner. Notably, the Chambers have seen fit to ignore the legal issues as non-issues, sought to sidestep properly addressing non-states parties’ objections by grounding jurisdictional authority in an asserted objective legal personality and further relied upon a conceptualization of the Court as an institution that acts on behalf of the international community as a whole to expansively interpret its scope of jurisdiction, without addressing the potential legal consequences for non-states parties. In so doing, the Chambers have significantly infringed the legal rights of non-states parties without persuasively establishing the legal authority to do so. The import of this failure on the part of Chambers has had detrimental consequences for the Court. The lack of legal clarity surrounding the Court’s relationship with non-state party nationals has emboldened non-states parties’ objections of illegitimacy and muted the effectiveness of the Court’s responses to those objections. The Court is unable to reference persuasive judicial rationales in response.
Epigenetic regulation of energy metabolism in obesity
Authors: Gao Wei , Liu Jia-Li , Lu Xiang , Yang Qin 
Published: July 2021

Abstract
Obesity has reached epidemic proportions globally. Although modern adoption of a sedentary lifestyle coupled with energy-dense nutrition is considered to be the main cause of obesity epidemic, genetic preposition contributes significantly to the imbalanced energy metabolism in obesity. However, the variants of genetic loci identified from large-scale genetic studies do not appear to fully explain the rapid increase in obesity epidemic in the last four to five decades. Recent advancements of next-generation sequencing technologies and studies of tissue-specific effects of epigenetic factors in metabolic organs have significantly advanced our understanding of epigenetic regulation of energy metabolism in obesity. The epigenome, including DNA methylation, histone modifications, and RNA-mediated processes, is characterized as mitotically or meiotically heritable changes in gene function without alteration of DNA sequence. Importantly, epigenetic modifications are reversible. Therefore, comprehensively understanding the landscape of epigenetic regulation of energy metabolism could unravel novel molecular targets for obesity treatment. In this review, we summarize the current knowledge on the roles of DNA methylation, histone modifications such as methylation and acetylation, and RNA-mediated processes in regulating energy metabolism. We also discuss the effects of lifestyle modifications and therapeutic agents on epigenetic regulation of energy metabolism in obesity.