bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-Targeting of MDM2 and CDK4/6 with Siremadlin and Ribociclib for the Treatment of Patients with Well-Differentiated or Dedifferentiated Liposarcoma: Results from a Proof-of-Concept, Phase Ib Study
Authors: Abdul Razak Albiruni R. , Bauer Sebastian , Suarez Cristina , Lin Chia-Chi , Quek Richard , Hütter-Krönke Marie Luise , Cubedo Ricardo , Ferretti Stephane , Guerreiro Nelson , Jullion Astrid , Orlando Elena J. , Clementi Giorgia , Sand Dejmek Janna , Halilovic Ensar , Fabre Claire , Blay Jean-Yves , Italiano Antoine
Published: December 2021

Purpose:

Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are characterized by co-amplification of the murine double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) oncogenes. Siremadlin, a p53–MDM2 inhibitor, was combined with ribociclib, a CDK4/6 inhibitor, in patients with locally advanced/metastatic WDLPS or DDLPS who had radiologically progressed on, or despite, prior systemic therapy.

Patients and Methods:

In this proof-of-concept, phase Ib, dose-escalation study, patients received siremadlin and ribociclib across different regimens until unacceptable toxicity, disease progression, and/or treatment discontinuation: Regimen A [4-week cycle: siremadlin once daily (QD) and ribociclib QD (2 weeks on, 2 weeks off)], Regimen B [3-week cycle: siremadlin once every 3 weeks; ribociclib QD (2 weeks on, 1 week off)], and Regimen C [4-week cycle: siremadlin once every 4 weeks; ribociclib QD (2 weeks on, 2 weeks off)]. The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of siremadlin plus ribociclib in one or more regimens.

Results:

As of October 16, 2019 (last patient last visit), 74 patients had enrolled. Median duration of exposure was 13 (range, 1–174) weeks. Dose-limiting toxicities occurred in 10 patients, most of which were Grade 3/4 hematologic events. The RDE was siremadlin 120 mg every 3 weeks plus ribociclib 200 mg QD (Regimen B). Three patients achieved a partial response, and 38 achieved stable disease. One patient (Regimen C) died as a result of treatment-related hematotoxicity.

Conclusions:

Siremadlin plus ribociclib demonstrated manageable toxicity and early signs of antitumor activity in patients with advanced WDLPS or DDLPS.
Paulo Freire: a cidadania compreensiva
Authors: Paiva Raquel
Published: December 2021

O texto apresenta o conceito de epistemologia compreensiva como um legado dos ensinamentos do educador Paulo Freire, cujo centenário se comemora em 2021. A proposta está centrada na cidadania como possibilidade a ser alcançada e exercida no quotidiano, a partir não apenas da ideia de conscientização, mas principalmente de sensibilização. O sensível como força motriz capaz de produzir a definitiva vinculação entre as diversidades e a convivialidade harmônica entre as diferenças, vislumbrando-se a construção do horizonte utópico freiriano. Diante da constatação de falência do arcabouço das ordens e paradigmas racionais, elege-se o sensorium como instância capaz de produzir novas formas de cidadania e do sensível como força geradora.
Conhecer é agir: entre a epistemologia genética e o legado de Paulo Freire
Authors: González Jorge A.
Published: December 2021

O que significa se tornar sujeitos do conhecimento? Atores sociais que enfrentam seus problemas por meio da construção de conhecimentos realmente se empoderam? A teoria e os achados da Epistemologia Genética fornecem uma poderosa ferramenta teórica e metodológica para compreender experiências de conscientização como processos de empoderamento, e permitem ler o método freiriano de alfabetização à luz de uma teoria dos processos de construção do conhecimento. Ao estudar e praticar a Comunicação para o Desenvolvimento, afirmo que Informação, Comunicação e Conhecimento constituem um processo tríplice e indissociável, que inclui transformações biológicas, comportamentais e sociais, especialmente as que foram criadas coletivamente.
Por uma singularidade da Geografia: desenvolvimento do Pensamento Geográfico
Authors: Santos Luline Silva Carvalho
Published: December 2021

A literatura contemporânea tem evocado como singularidade da Geografia a estruturação de uma forma de pensar específica denominada Pensamento Geográfico. Todavia, se há uma ampla defesa da Geografia como forma de pensar, contraditoriamente, ainda são poucos os trabalhos que conceituam o que é esse Pensamento Geográfico, seus processos de estruturação e constituição. Este artigo visa contribuir com o avanço do debate teórico reduzindo a lacuna sobre o tema na literatura brasileira. A discussão está balizada nas seguintes questões: o que é o Pensamento Geográfico? Como se desenvolve? Que processos cognitivos o caracterizam? Para tanto, realizou-se pesquisa bibliográfica nos campos da Psicologia e da Geografia relacionando a cognição humana e suas especificidades a partir da aprendizagem e da formação dos conceitos geográficos pelos indivíduos. Por fim, observou-se como essa relação culmina na constituição de uma forma singular de pensar.
Tectônica global em livros didáticos de geografia da 1ª série do Ensino Médio: uma análise do conteúdo
Authors: Souza Alexandre dos Santos , Furrier Max
Published: December 2021

Os livros didáticos de Geografia abordam a Tectônica Global desde o 6º ano do Ensino Fundamental, mas é na 1ª série do Ensino Médio que se enfatiza o tema. Este artigo analisa a qualidade das representações imagéticas e textuais sobre a Teoria da Tectônica Global presentes nos 14 livros didáticos de Geografia da 1º série do Ensino Médio distribuídos pelo Programa Nacional do Livro Didático no triênio de 2018-2020. Para tanto, se quantificaram e qualificaram as informações, observando se fornecem subsídios claros e corretos que auxiliem o ensino de Geografia na Educação Básica. Verificou-se que a apresentação do tema demanda correções fundamentais e, em alguns livros, constatou-se a falta de informações relevantes como, por exemplo, a sismicidade existente no território brasileiro. Assim, este trabalho visa concorrer para a melhoria dos livros didáticos brasileiros propondo correções, ajustes e sugestões baseadas em bibliografia especializada, mas sem verticalizações conceituais que poderiam fugir ao escopo desse tema destinado ao Ensino Médio.
Redes globais de produção: um caminho de análise para a geografia econômica
Authors: Bezerra Juscelino Eudâmidas
Published: December 2021

Reconhecer a complexidade da economia global pressupõe um olhar abrangente ao modo como a ciência geográfica pode contribuir para explicar as relações econômicas, sociais e de poder que operam simultaneamente em múltiplas escalas. O objetivo do artigo é perscrutar o conceito de redes globais de produção (RGP) como um caminho de análise para a geografia econômica a partir dos estudos pioneiros da Escola de Geografia Econômica de Manchester. A organização das redes globais de produção estrutura-se na questão do valor e em sua trajetória, na caracterização dos atores e em sua diversidade, assim como na configuração de redes e territorialidades. O texto também procura entender a dinâmica de organização da economia global a partir de uma análise centrada na agência dos atores, particularmente as empresas líderes, suas estratégias e dinâmicas competitivas, com a finalidade máxima de alcançar o desenvolvimento regional e a superação das desigualdades.
Culturas que também se expressam em português: formação de leitores por meio de poemas africanos na EJA
Authors: Inácio Emerson da Cruz , Barreto Fábio Roberto Ferreira
Published: December 2021

Trata-se de experiência atinente à formação de leitores por meio de poemas de literatura africana, que se desenvolveu no projeto, de cunho interdisciplinar e étnicoracial, Culturas Que Também Se Expressam Em Português com turmas de EJA (Educação de Jovens e Adultos) da escola pública EMEF CEU Cantos do Amanhecer, da DRE-CL (Diretoria de Ensino de Campo Limpo), da Secretaria Municipal de Educação de São Paulo, em 2016.
Reflexões acerca do lugar dos estudos de vertente formal do conto de fadas no contexto do sistema literário e face aos desenvolvimentos atuais da área de LIJ
Authors: Garcia André Luiz Ming , Bernheimer Kate
Published: December 2021

Ensaio crítico e introdutório escrito pelo prof. André Luiz Ming Garcia seguido da tradução comentada do texto "Fairy tale is form, form is fairy tale" de Kate Benheimer.
A semelhança da música com a linguagem segundo Theodor Adorno: sentidos diferentes do conceito a partir da música tradicional e da nova música
Authors: Andrade Luis Filipe de Lima
Published: December 2021

Este artigo investiga a concepção de semelhança da música com a linguagem na estética musical de Adorno. Partindo de uma descrição e fundamentação histórica do conceito, o objetivo principal deste artigo consiste na defesa de que o conceito se concebe de modo especifico na música tradicional (tonalidade), por um lado, e na nova música, por outro lado. Desse modo, argumentaremos que, apesar de a nova música ter se rebelado contra o conceito, ele permaneceria presente em sua estrutura, pois, ao fim, ele seria condição para a constituição de um elemento fundamental da música, a saber, o nexo de sentido.
PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle
Authors: Wu Tongbin , Liang Zhengyu , Zhang Zengming , Liu Canzhao , Zhang Lunfeng , Gu Yusu , Peterson Kirk L. , Evans Sylvia M. , Fu Xiang-Dong , Chen Ju
Published: December 2021

Background:

Left ventricular noncompaction cardiomyopathy (LVNC) was discovered half a century ago as a cardiomyopathy with excessive trabeculation and a thin ventricular wall. In the decades since, numerous studies have demonstrated that LVNC primarily has an effect on left ventricles (LVs) and is often associated with LV dilation and dysfunction. However, in part because of the lack of suitable mouse models that faithfully mirror the selective LV vulnerability in patients, mechanisms underlying the susceptibility of LVs to dilation and dysfunction in LVNC remain unknown. Genetic studies have revealed that deletions and mutations in
PRDM16
(PR domain-containing 16) cause LVNC, but previous conditional
Prdm16
knockout mouse models do not mirror the LVNC phenotype in patients, and the underlying molecular mechanisms by which PRDM16 deficiency causes LVNC are still unclear.

Methods:

Prdm16
cardiomyocyte–specific knockout (
Prdm16

cKO

) mice were generated and analyzed for cardiac phenotypes. RNA sequencing and chromatin immunoprecipitation deep sequencing were performed to identify direct transcriptional targets of PRDM16 in cardiomyocytes. Single-cell RNA sequencing in combination with spatial transcriptomics was used to determine cardiomyocyte identity at the single-cell level.

Results:

Cardiomyocyte-specific ablation of
Prdm16
in mice caused LV-specific dilation and dysfunction, as well as biventricular noncompaction, which fully recapitulated LVNC in patients. PRDM16 functioned mechanistically as a compact myocardium-enriched transcription factor that activated compact myocardial genes while repressing trabecular myocardial genes in LV compact myocardium. Consequently,
Prdm16

cKO

LV compact myocardial cardiomyocytes shifted from their normal transcriptomic identity to a transcriptional signature resembling trabecular myocardial cardiomyocytes or neurons. Chamber-specific transcriptional regulation by PRDM16 was attributable in part to its cooperation with LV-enriched transcription factors Tbx5 and Hand1.

Conclusions:

These results demonstrate that disruption of proper specification of compact cardiomyocytes may play a key role in the pathogenesis of LVNC. They also shed light on underlying mechanisms of the LV-restricted transcriptional program governing LV chamber growth and maturation, providing a tangible explanation for the susceptibility of LV in a subset of LVNC cardiomyopathies.
Faith in Drugs: The Material and Immaterial Effects of Medication in the Early Modern French Catholic World
Authors: Rivest Justin
Published: December 2021

This article explores a set of medications, called les remèdes des pauvres, that were distributed from the late seventeenth century onward to the sick poor of rural France and to French missions abroad. Although it was eventually absorbed into the French state as a form of royally sponsored poor relief, this drug distribution network began in 1670 as a distinctly ecclesiastical endeavour, aimed at allowing parish priests, missionaries, and charitable laywomen to imitate the healing ministry of Christ and his apostles. While critics saw them as peddling a dangerous chemical drug in poor villages, their promoters argued that the active charity involved in distributing the remedies, and even the faith placed in their effectiveness by the sick, played an important role in effecting their cures. As such they offer a useful perspective on the shifting boundaries between medical charity and medical commerce, as well as between natural and supernatural healing.
“The Bush Burned with Fire and the Bush Was Not Consumed”
Authors: Feldmann Kaye Miriam
Published: December 2021

This paper explores the post-metaphysical theology of Richard Kearney (1954–) from a Jewish theological perspective. It seeks to provide an original analysis of his project “anatheism,” considering the prominence of Jewish texts in the development of the concept of anatheism. Rooted in deconstructionist and Continental philosophical discourses, Jewish hermeneutics also plays a central role in anatheism. This discursive intersection has received scarce scholarly attention to date. Biblical and other texts which he interprets, include the rabbinic exegesis of Rashi and of modern Jewish hermeneutical philosophy notably of Martin Buber, Franz Rosenzweig, and Emmanuel Levinas. I analyse elements of Kearney’s interpretation primarily of the “Burning Bush” biblical narrative as a test case for anatheistic reading of Jewish texts as they appear in one particular text “I Am Who May Be” in The God Who May Be: A Hermeneutics of Religion (2001). Kearney’s textual reading of the Burning Bush offers an unusual example of a Christian engagement with Jewish interpretations of the biblical parable as well as of Levinas, Derrida, and others. Kearney’s effort highlights an approach of a mutual search for ways of interpreting texts not “of” the other, but “with” the other, in a mutual engagement of post-metaphysical theology. More broadly, this examination offers an important contribution to the developing field of post-metaphysical theology in the Jewish and Christian traditions, ultimately posing questions as to how and whether elements of Jewish scriptural interpretative techniques might or can imbue contemporary Christian post-metaphysical theologies. Conversely, the question can be asked as to what a Jewish version of anatheism might look like. This examination presents a test case for possibilities of reading and learning from discourses across different religions.
Allied but Deviating NATO in the Multipolar World
Authors: Ozkaleli Ferit Murat , Gunes Ali
Published: December 2021

“How long can NATO last in a post-US hegemonic, multipolar world?” has become an important question in contemporary world politics. By statistically analyzing NATO alliance cohesion since its inception, this analysis contributes to the literature by developing an original set of indicators that rely on the ideal point estimates from a recent UN General Assembly voting dataset. It empirically verifies that NATO members have higher cohesion than other UN members, although the United States has been the most significant deviating member since 1980. The findings support some earlier proposals such as the external threat hypothesis. They also contradict some others, notably the literature on the Donald Trump administration’s withdrawal doctrine, and the decline of US hegemony and its policy implications. The article concludes that the future challenge for NATO cohesion not only would be the possibility of US abdication or abandonment, but also other members’ balancing the United States as the hegemon.
Pre-Eminent or Subordinate? An Organisational Environment Perspective on the EU’s Security Cooperation with asean and ecowas
Authors: Müller Lukas Maximilian
Published: December 2021

Security cooperation with other regional organisations (ros) has long been a facet of EU foreign policy. The EU’s relationships with the Association of Southeast Asian Nations (asean) and the Economic Community of West African States (ecowas) illustrate the variety of the EU’s engagement. In West Africa, the EU is a pre-eminent actor, occasionally dictating an agenda and marginalising ecowas. In Southeast Asia, the EU remains subordinate, facing an uphill battle for relevance in the security sphere and a closer relationship to asean. Prevailing explanations focus on the EU’s internal characteristics or bilateral cooperation dynamics, but fail to fully explain this discrepancy. Based on new interview information, this article argues that the organisational environment also affects the EU’s security cooperation with asean and ecowas. The presence of competitive environments limits the EU’s role in security cooperation and relegates it to a subordinate role. In the absence of competition, the EU is allowed to become pre-eminent.
A Challenge to the Liberal Peace? European Union Peacebuilding faces China in Nepal
Authors: Strasheim Julia , Bogati Subindra
Published: December 2021

How does China’s rising presence in Nepal affect the European Union’s own peacebuilding efforts in the country? As a global peace and security actor, the EU has followed the liberal peacebuilding model that promotes peace by strengthening democratic institutions. China’s rise as a “pragmatic” peacebuilder is often called non-conducive to this approach, but how this dynamic plays out has rarely been studied with detailed case evidence. We narrow this gap using the case of Nepal. Drawing on interviews conducted between 2015 and 2020, we find that China’s rise has decreased the EU’s leverage in promoting peace in the areas of civil society, human rights, and constitution-building. But some setbacks in the peace process were unrelated to China. Instead, they were also linked to the EU’s own reform neglects and policy differences, and to local perceptions about peacebuilders, showing how external and internal challenges jointly affect the EU’s role as peacebuilder.
The Arbitration Panel Report in Ukraine – Export Prohibition on Wood Products: Lessons from the ‘Pegasus’ of International Adjudication
Authors: Pogoretskyy Vitaliy
Published: December 2021

The Arbitration Panel’s decision in Ukraine – Export Prohibition on Wood Products suggests the emerging trend among some Word Trade Organization (WTO) Members to settle their trade irritants regionally. This dispute was adjudicated between the EU and Ukraine, which are both WTO Members, under the WTO rules that are incorporated by reference into the Association Agreement between these parties and by the Arbitration Panel the two members of which are well-known WTO adjudicators. The dispute settlement proceedings in this case thus illustrate how regional dispute settlement mechanisms work in practice and shed some light on whether these mechanisms could serve as a viable alternative to the WTO at the time of the ongoing WTO dispute settlement crisis. Moreover, from a substantive perspective, some may view this decision as an important milestone in international economic law, which contributes to the long-standing debate on how the right balance should be struck between trade and environmental considerations, in this case, the conservation of forests. This article, however, addresses several important shortcomings in the Arbitration Panel’s reasoning, which appear to diminish the relevance of the decision beyond the dispute at hand.
Law of the Sea and the Pandemic—Humanitarian Principles under Siege?
Authors: Mossop Joanna
Published: December 2021

In the COVID-19 pandemic two particular issues have arisen in relation to borders and the law of the sea: the right of ships—particularly cruise ships—to enter port and the ongoing restrictions on seafarers aboard merchant ships. In these cases, the sovereign interests of states in preventing the spread of a dangerous virus have been pitted against the humanitarian interests of those onboard the vessels. This article first describes the humanitarian concerns created by states’ responses to the emergence of COVID-19. It then discusses the various legal principles that apply to the situation, primarily the International Health Regulations, the doctrine of distress and the Maritime Labour Convention. Finally, it considers whether any lessons can be learned from this experience to hopefully lessen humanitarian problems if another pandemic happens in the future.
International Human Rights Law and the Protection of Medical Scientists against State Inference during COVID-19
Authors: Liljeblad Jonathan
Published: December 2021

The global COVID-19 pandemic has hosted a rising trend of state interference in medical science research against the virus. Such illiberal actions are counterproductive to hopes of addressing the virus because they impede the operations of scientific inquiry and threaten the integrity of scientific findings. State efforts to interfere in pandemic science work involve constraints upon medical scientists researching the virus. Such constraints risk violating the human rights of the scientists involved in COVID-19 research. International human rights law provides means of protecting scientists against state interference, and the reach of international human rights instruments approaches a scale comparable to the global reach of the pandemic. As a result, the exercise of international human rights law on behalf of medical scientists against state interference furthers the global urgency to resolve the COVID-19 pandemic.
The UN Security Council’s Response to COVID-19: From the Centre to the Periphery?
Authors: Farrall Jeremy , Michaelsen Christopher
Published: December 2021

This article examines the UN Security Council’s response to the escalating COVID-19 pandemic in 2020, which has been criticised as hesitant and half-hearted. It argues that the Council’s inability to respond more assertively to the COVID threat was more predictable than surprising. Indeed, the Council’s approach to the COVID threat tended to follow, rather than diverge from, its past practice, exhibiting three increasingly entrenched features of Council decision-making in a crisis. First, the Council is hesitant and ill-equipped to respond to non-traditional or unorthodox threats to international peace and security, even where relevant precedents exist to support such a response. Second, the Council struggles to act when there is friction between permanent members. Third, when all else fails, the Council can still do reliably well on process.
Drawing Lines at Sea: Australia’s Five Decades of Maritime Boundary Delimitation
Authors: Østhagen Andreas
Published: December 2021

Boundaries in the ocean are man-made constructs of importance to everything from oil and gas production, to fisheries and environmental protection. How do states delineate such ownership and rights? These are the core questions examined in this article, which studies Australia’s maritime boundary agreements, starting with Indonesia in 1971 and ending with Timor-Leste in 2019. In addition to depicting and documenting the main drivers and impediments to these agreements whenever Australia has had to negotiate with a third country, it examines Australia’s approach to boundary-making at sea more generally. Drawing on international law and political science, this article shows why we need understand the interplay between security politics, legal considerations and domestic interests in order to understand what motivates states to settle their maritime disputes.
The genus Diplectrona Westwood (Trichoptera: Hydropsychidae) in the Japanese main islands
Authors: NOZAKI TAKAO
Published: December 2021

The genus Diplectrona Westwood (Trichoptera: Hydropsychidae) is revised for the Japanese main islands, and four species are recognized, the three species D. aiensis Kobayashi, D. burha Schmid, and D. kibuneana Tsuda, and one new species, D. takaii sp. nov. Diplectrona difficultata (Kobayashi) is synonymized with D. kibuneana. Diplectrona japonica Banks and D. albomarginata Ulmer are transferred to the genus Homoplectra Ross.
Emergent Constraints on CMIP6 Climate Warming Projections: Contrasting Cloud- and Surface Temperature–Based Constraints
Authors: Liang Yongxiao , Gillett Nathan P. , Monahan Adam H.
Published: December 2021

The latest Coupled Model Intercomparison Project (CMIP6) multimodel ensemble shows a broader range of projected warming than the previous-generation CMIP5 ensemble. We show that the projected warming is well correlated with tropical and subtropical low-level cloud properties. These physically meaningful relations enable us to use observed cloud properties to constrain future climate warming. We develop multivariate linear regression models with metrics selected from a set of potential constraints based on a stepwise selection approach. The resulting linear regression model using two low-cloud metrics shows better cross-validated results than regression models that use single metrics as constraints. Application of a regression model using the low-cloud metrics to climate projections results in similar estimates of the mean, but substantially narrower uncertainty ranges, of projected twenty-first-century warming when compared with unconstrained simulations. The resulting projected global-mean warming in 2081–2100 relative to 1995–2014 is 2.84–5.12 K (5%–95% range) for Shared Socioeconomic Pathway (SSP) 5–8.5 compared with a range of 2.34–5.81 K for unconstrained projections, and 0.60–1.70 K for SSP1–2.6 compared to an unconstrained range of 0.38–2.04 K. We provide evidence for a higher lower bound of the projected warming range than that obtained from constrained projections based on the past global-mean temperature trend. Consideration of the impact of the sea surface temperature pattern effect on the recent observed warming trend, which is not well captured in the CMIP6 ensemble, indicates that the relatively low projected warming resulting from the global-mean temperature trend constraint may not be reliable and provides further justification for the use of climatologically based cloud metrics to constrain projections.
Dynasties in the making: Family wealth and inheritance for the first-generation ultra-wealthy and their wealth managers
Authors: Higgins Katie
Published: December 2021

The inheritance practices of the ultra-wealthy play a key role in reproducing socio-economic inequalities across generations. Given this role, we need a better understanding of the individuals and families who own, accumulate and pass on substantial amounts of wealth. This article asks two questions: first, how do parents with profound ownership or control over capital reconcile cultivating dynastic wealth with beliefs in meritocratic achievement? And, second, how do wealth managers justify their commercial value to first generation wealthy clients? The answer to both of these questions involves what I call a pedagogy of inherited wealth. Drawing on semi-structured interviews with first-generation ultra-wealthy parents and their wealth managers, it documents how wealthy parents and wealth managers construct risky futures around inheritance, and their strategies to manage those risks through the control of access to the family’s wealth. In doing so, it explores how they produce two roles, termed here the ‘good inheritor’ and the ‘good client’. Through examining various strategies to manage family wealth and inheritance, the article reveals the legitimating and enabling pedagogy surrounding this process and the paradox at the heart of this pedagogy – which promotes both the value of work among the next generation of inheritors and the preservation of dynastic wealth that will preclude their dependence on income-generating work.
Prospective comparison of magnetic resonance imaging and computed tomography in diagnosing occult scaphoid fractures
Authors: Sahu Ajay , Kuek Dorothy KC , MacCormick Andrew , Gozzard Charles , Ninan Tishi , Fullilove Sue , Suresh Priya
Published: December 2021

Background

Suspected scaphoid fracture (SF) after a fall on an outstretched hand is a common presentation in the emergency department. Magnetic resonance imaging (MRI) or computed tomography (CT) has been suggested to assist in the diagnosis or exclusion of SF.

Purpose

To compare MRI and CT at diagnosing occult SFs.

Material and Methods

We routinely perform CT scans in patients with clinically suspected occult SF, after 7–10 days of injury following two negative radiographs. All eligible patients with a clinically suspected SF, but negative radiographs and a negative CT, underwent an MRI scan to assess further for evidence of occult fracture.

Results

A total of 100 patients were included in our study. MRI showed fractures in 16% of the time (in 15 patients) when plain radiographs and CT did not. Of these fractures, 8% were SFs. In addition to fractures, 10% had bone bruising. A total of 25% of patients with fractures and bone bruising were referred to the hand surgery team for further follow-up.

Conclusion

The study demonstrated that MRI would identify a radiographically occult SF more often than CT. This supports NICE guidelines which recommend MRI as the best early diagnostic tool for occult SFs.
Improving deep learning method for biomedical named entity recognition by using entity definition information
Authors: Xiong Ying , Chen Shuai , Tang Buzhou , Chen Qingcai , Wang Xiaolong , Yan Jun , Zhou Yi
Published: December 2021

Background

Biomedical named entity recognition (NER) is a fundamental task of biomedical text mining that finds the boundaries of entity mentions in biomedical text and determines their entity type. To accelerate the development of biomedical NER techniques in Spanish, the PharmaCoNER organizers launched a competition to recognize pharmacological substances, compounds, and proteins. Biomedical NER is usually recognized as a sequence labeling task, and almost all state-of-the-art sequence labeling methods ignore the meaning of different entity types. In this paper, we investigate some methods to introduce the meaning of entity types in deep learning methods for biomedical NER and apply them to the PharmaCoNER 2019 challenge. The meaning of each entity type is represented by its definition information.

Material and method

We investigate how to use entity definition information in the following two methods: (1) SQuad-style machine reading comprehension (MRC) methods that treat entity definition information as query and biomedical text as context and predict answer spans as entities. (2) Span-level one-pass (SOne) methods that predict entity spans of one type by one type and introduce entity type meaning, which is represented by entity definition information. All models are trained and tested on the PharmaCoNER 2019 corpus, and their performance is evaluated by strict micro-average precision, recall, and F1-score.

Results

Entity definition information brings improvements to both SQuad-style MRC and SOne methods by about 0.003 in micro-averaged F1-score. The SQuad-style MRC model using entity definition information as query achieves the best performance with a micro-averaged precision of 0.9225, a recall of 0.9050, and an F1-score of 0.9137, respectively. It outperforms the best model of the PharmaCoNER 2019 challenge by 0.0032 in F1-score. Compared with the state-of-the-art model without using manually-crafted features, our model obtains a 1% improvement in F1-score, which is significant. These results indicate that entity definition information is useful for deep learning methods on biomedical NER.

Conclusion

Our entity definition information enhanced models achieve the state-of-the-art micro-average F1 score of 0.9137, which implies that entity definition information has a positive impact on biomedical NER detection. In the future, we will explore more entity definition information from knowledge graph.
Analyzing transfer learning impact in biomedical cross-lingual named entity recognition and normalization
Authors: Rivera-Zavala Renzo M. , Martínez Paloma
Published: December 2021

Background

The volume of biomedical literature and clinical data is growing at an exponential rate. Therefore, efficient access to data described in unstructured biomedical texts is a crucial task for the biomedical industry and research. Named Entity Recognition (NER) is the first step for information and knowledge acquisition when we deal with unstructured texts. Recent NER approaches use contextualized word representations as input for a downstream classification task. However, distributed word vectors (embeddings) are very limited in Spanish and even more for the biomedical domain.

Methods

In this work, we develop several biomedical Spanish word representations, and we introduce two Deep Learning approaches for pharmaceutical, chemical, and other biomedical entities recognition in Spanish clinical case texts and biomedical texts, one based on a Bi-STM-CRF model and the other on a BERT-based architecture.

Results

Several Spanish biomedical embeddigns together with the two deep learning models were evaluated on the PharmaCoNER and CORD-19 datasets. The PharmaCoNER dataset is composed of a set of Spanish clinical cases annotated with drugs, chemical compounds and pharmacological substances; our extended Bi-LSTM-CRF model obtains an F-score of 85.24% on entity identification and classification and the BERT model obtains an F-score of 88.80% . For the entity normalization task, the extended Bi-LSTM-CRF model achieves an F-score of 72.85% and the BERT model achieves 79.97%. The CORD-19 dataset consists of scholarly articles written in English annotated with biomedical concepts such as disorder, species, chemical or drugs, gene and protein, enzyme and anatomy. Bi-LSTM-CRF model and BERT model obtain an F-measure of 78.23% and 78.86% on entity identification and classification, respectively on the CORD-19 dataset.

Conclusion

These results prove that deep learning models with in-domain knowledge learned from large-scale datasets highly improve named entity recognition performance. Moreover, contextualized representations help to understand complexities and ambiguity inherent to biomedical texts. Embeddings based on word, concepts, senses, etc. other than those for English are required to improve NER tasks in other languages.
Deep learning with language models improves named entity recognition for PharmaCoNER
Authors: Sun Cong , Yang Zhihao , Wang Lei , Zhang Yin , Lin Hongfei , Wang Jian
Published: December 2021

Background

The recognition of pharmacological substances, compounds and proteins is essential for biomedical relation extraction, knowledge graph construction, drug discovery, as well as medical question answering. Although considerable efforts have been made to recognize biomedical entities in English texts, to date, only few limited attempts were made to recognize them from biomedical texts in other languages. PharmaCoNER is a named entity recognition challenge to recognize pharmacological entities from Spanish texts. Because there are currently abundant resources in the field of natural language processing, how to leverage these resources to the PharmaCoNER challenge is a meaningful study.

Methods

Inspired by the success of deep learning with language models, we compare and explore various representative BERT models to promote the development of the PharmaCoNER task.

Results

The experimental results show that deep learning with language models can effectively improve model performance on the PharmaCoNER dataset. Our method achieves state-of-the-art performance on the PharmaCoNER dataset, with a max F1-score of 92.01%.

Conclusion

For the BERT models on the PharmaCoNER dataset, biomedical domain knowledge has a greater impact on model performance than the native language (i.e., Spanish). The BERT models can obtain competitive performance by using WordPiece to alleviate the out of vocabulary limitation. The performance on the BERT model can be further improved by constructing a specific vocabulary based on domain knowledge. Moreover, the character case also has a certain impact on model performance.
Histogram analysis of dynamic contrast-enhanced magnetic resonance imaging in the differential diagnosis of parotid tumors
Authors: Xiang Shiyu , Ren Jiliang , Xia Zhipeng , Yuan Ying , Tao Xiaofeng
Published: December 2021

Objective

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) histograms were used to investigate whether their parameters can distinguish between benign and malignant parotid gland tumors and further differentiate tumor subgroups.

Materials and methods

A total of 117 patients (32 malignant and 85 benign) who had undergone DCE-MRI for pretreatment evaluation were retrospectively included. Histogram parameters including mean, median, entropy, skewness, kurtosis and 10th, 90th percentiles were calculated from time to peak (TTP) (s), wash in rate (WIR) (l/s), wash out rate (WOR) (l/s), and maximum relative enhancement (MRE) (%) mono-exponential models. The Mann–Whitney U test was used to compare the differences between the benign and malignant groups. The diagnostic value of each significant parameter was determined on Receiver operating characteristic (ROC) analysis. Multivariate stepwise logistic regression analysis was used to identify the independent predictors of the different tumor groups.

Results

For both the benign and malignant groups and the comparisons among the subgroups, the parameters of TTP and MRE showed better performance among the various parameters. WOR can be used as an indicator to distinguish Warthin’s tumors from other tumors. Warthin’s tumors showed significantly lower values on 10th MRE and significantly higher values on skewness TTP and 10th WOR, and the combination of 10th MRE, skewness TTP and 10th WOR showed optimal diagnostic performance (AUC, 0.971) and provided 93.12% sensitivity and 96.70% specificity. After Warthin’s tumors were removed from among the benign tumors, malignant parotid tumors showed significantly lower values on the 10th TTP (AUC, 0.847; sensitivity 90.62%; specificity 69.09%; P < 0.05) and higher values on skewness MRE (AUC, 0.777; sensitivity 71.87%; specificity 76.36%; P < 0.05).

Conclusion

DCE-MRI histogram parameters, especially TTP and MRE parameters, show promise as effective indicators for identifying and classifying parotid tumors. Entropy TTP and kurtosis MRE were found to be independent differentiating variables for malignant parotid gland tumors. The 10th WOR can be used as an indicator to distinguish Warthin’s tumors from other tumors.
Is the healthy start scheme associated with increased food expenditure in low-income families with young children in the United Kingdom?
Authors: Parnham Jennie , Millett Christopher , Chang Kiara , Laverty Anthony A. , von Hinke Stephanie , Pearson-Stuttard Jonathan , Vamos Eszter P.
Published: December 2021

Background

Healthy Start is a food assistance programme in the United Kingdom (UK) which aims to provide a nutritional safety-net and enable low-income families on welfare benefits to access a healthier diet through the provision of food vouchers. Healthy Start was launched in 2006 but remains under-evaluated. This study aims to determine whether participation in the Healthy Start scheme is associated with differences in food expenditure in a nationally representative sample of households in the UK.

Methods

Cross-sectional analyses of the Living Costs and Food Survey dataset (2010–2017). All households with a child (0–3 years) or pregnant woman were included in the analysis (n = 4869). Multivariable quantile regression compared the expenditure and quantity of fruit and vegetables (FV), infant formula and total food purchases. Four exposure groups were defined based on eligibility, participation and income (Healthy Start Participating, Eligible Non-participating, Nearly Eligible low-income and Ineligible high-income households).

Results

Of 876 eligible households, 54% participated in Healthy Start. No statistically significant differences were found in FV or total food purchases between participating and eligible non-participating households, but infant formula purchases were lower in Healthy Start participating households. Ineligible higher-income households had higher purchases of FV.

Conclusion

This study did not find evidence of an association between Healthy Start participation and FV expenditure. Moreover, inequalities in FV purchasing persist in the UK. Higher participation and increased voucher value may help to improve programme performance and counteract the harmful effects of poverty on diet.
Intimate partner violence during COVID-19 lockdown in Norway: the increase of police reports
Authors: Nesset Merete Berg , Gudde Camilla Buch , Mentzoni Gro Elisabet , Palmstierna Tom
Published: December 2021

Background

In March 2020, the Norwegian government announced a COVID-19 lockdown in order to reduce the spread of the coronavirus. In Norway, lockdown measures included restricting people’s ability to leave their home and the closing of social institutions, thus reducing the capacity for victims of intimate partner violence to alert someone outside of their home about violent incidents that occurred during lockdown. At the same time, the restrictive measures forced the victim and the perpetrator to stay together for prolonged periods within the home, and reduced the possibility for them to escape or leave the perpetrator. The aim of this study was to investigate how the frequency and character of intimate partner violence reported to the police changed during the period of lockdown in Norway.

Methods

All cases of intimate partner violence registered in police files before the pandemic (from January 2016-February 2020) and during lockdown in Norway (March-December 2020) were included in the study, representing a total of 974 cases. Differences in the number and severity of cases were calculated using χ2-tests and Wilcoxon’s rank sum test. Differences in the characteristics of the reported violence was assessed with the Brief Spousal Assault form for the Evaluation of Risk (B-SAFER) and tested with Fischer’s exact test with Bonferroni correction. Standardised Morbidity Rate (SMR) statistics were used to analyse the proportion of immigrants as compared to the general population.

Results

Reported intimate partner violence increased by 54% during the lockdown period in Norway. Between March-December 2020, the police assessed the cases as being at higher risk of imminent and severe violence. Our findings indicated an overrepresentation of immigrant perpetrators before and during lockdown (SMR = 1.814, 95% CI = 1.792–1.836 before, and SMR = 1.807, 95% CI = 1.742–1.872 during lockdown). Notably, while victims with an immigrant background were overrepresented before lockdown, we found significantly lower proportion of immigrant IPV victims during the lockdown period (SMR = 1.070, 95% CI = 1.052–1.087 before, and SMR = 0.835, CI 95% CI = 0.787-0.883 during lockdown). Also, there were significantly more female perpetrators and male victims reported to the police during the lockdown period. A higher proportion of the victims were assessed as having unsafe living conditions and personal problems during lockdown. Finally, during the lockdown period in Norway, a higher proportion of perpetrators had a history of intimate relationship problems.

Conclusions

Intimate partner violence increased dramatically during the COVID-19 lockdown. A range of options for victims to escape from their perpetrators, particularly during times of crisis, should be developed in line with good practice, and with a special focus on the most vulnerable victims.
Chronic hypersensitivity pneumonitis is associated with an increased risk of venous thromboembolism: a retrospective cohort study
Authors: Sobiecka Małgorzata , Szturmowicz Monika , Lewandowska Katarzyna , Kowalik Agata , Łyżwa Ewa , Zimna Katarzyna , Barańska Inga , Jakubowska Lilia , Kuś Jan , Langfort Renata , Tomkowski Witold
Published: December 2021

Background

Idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis share commonalities in pathogenesis shifting haemostasis balance towards the procoagulant and antifibrinolytic activity. Several studies have suggested an increased risk of venous thromboembolism in IPF. The association between venous thromboembolism and chronic hypersensitivity pneumonitis has not been studied yet.

Methods

A retrospective cohort study of IPF and chronic hypersensitivity pneumonitis patients diagnosed in single tertiary referral center between 2005 and 2018 was conducted. The incidence of symptomatic venous thromboembolism was evaluated. Risk factors for venous thromboembolism and survival among those with and without venous thromboembolism were assessed.

Results

A total of 411 (259 IPF and 152 chronic hypersensitivity) patients were included (mean age 66.7 ± 8.4 vs 51.0 ± 13.3 years, respectively). There were 12 (4.6%) incident cases of venous thromboembolism in IPF and 5 (3.3%) in chronic hypersensitivity pneumonitis cohort. The relative risk (RR) of venous thromboembolism in chronic hypersensitivity pneumonitis was not significantly different to that found in patients with IPF (7.1 vs 11.8/1000 person-years, RR 1.661 95% CI 0.545–6.019, respectively).

The treatment with systemic steroids (OR 5.38; 95% CI 1.65–18.8, p = 0.006) and GAP stage 3 (OR 7.85; 95% CI 1.49–34.9; p = 0.037) were significant risk factors for venous thromboembolism in IPF. Arterial hypertension and pulmonary hypertension significantly increased risk of venous thromboembolism in chronic hypersensitivity pneumonitis. There were no significant differences in survival between patients with and without venous thromboembolism.

Conclusions

The patients with chronic hypersensitivity pneumonitis have a marked increase in the risk of venous thromboembolism, similar to the patients with IPF. Venous thromboembolism does not affect the survival of patients with IPF and chronic hypersensitivity pneumonitis.
LRSCnet: Local Reference Semantic Code learning for breast tumor classification in ultrasound images
Authors: Zhang Guang , Ren Yanwei , Xi Xiaoming , Li Delin , Guo Jie , Li Xiaofeng , Tian Cuihuan , Xu Zunyi
Published: December 2021

Purpose

This study proposed a novel Local Reference Semantic Code (LRSC) network for automatic breast ultrasound image classification with few labeled data.

Methods

In the proposed network, the local structure extractor is firstly developed to learn the local reference which describes common local characteristics of tumors. After that, a two-stage hierarchical encoder is developed to encode the local structures of lesion into the high-level semantic code. Based on the learned semantic code, the self-matching layer is proposed for the final classification.

Results

In the experiment, the proposed method outperformed traditional classification methods and AUC (Area Under Curve), ACC (Accuracy), Sen (Sensitivity), Spec (Specificity), PPV (Positive Predictive Values), and NPV(Negative Predictive Values) are 0.9540, 0.9776, 0.9629, 0.93, 0.9774 and 0.9090, respectively. In addition, the proposed method also improved matching speed.

Conclusions

LRSC-network is proposed for breast ultrasound images classification with few labeled data. In the proposed network, a two-stage hierarchical encoder is introduced to learn high-level semantic code. The learned code contains more effective high-level classification information and is simpler, leading to better generalization ability.