bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Assessment of EPB Shield Construction Based on the Nonlinear FAHP Method
Authors: Wang Xueyan , Gong Hang , Song Qiyu , Yan Xiao , Luo Zheng
Published: April 2022

There are many risk factors in EPB shield construction. The traditional fuzzy analytic hierarchy process (FAHP) method usually uses a linear analysis method to determine the risk level, but there are often some risk factors with prominent influence, which will reduce the accuracy of the evaluation results. In this paper, a new risk assessment model of Earth pressure balance (EPB) shield construction based on a nonlinear FAHP method is established by introducing nonlinear factors into the comprehensive calculation of the traditional FAHP. First, the new model establishes the framework of EPB shield construction risk analysis based on the work breakdown structure (WBS) and risk breakdown structure (RBS) methods. Then, it constructs an EPB shield construction risk index system by coupling the units of the WBS and RBS. The model constructs a fuzzy consistent judgment matrix, which replaces the 1∼9 scale. Finally, the nonlinear operator is introduced into the FAHP comprehensive calculation, considering the influence of some prominent risk factors, which improves the accuracy of the risk assessment. By applying the new model to the risk analysis of the EPB shield construction section of a tunnel project in Hangzhou, the effectiveness of the model is further verified.
Functional Genomic Analysis ofCDK4andCDK6Gene Dependency across Human Cancer Cell Lines
Authors: Zhang Zhouwei , Golomb Lior , Meyerson Matthew
Published: April 2022

Cyclin-dependent kinase 4 (CDK4) and CDK6 are key cell-cycle regulators that are frequently dysregulated in human malignancies. CDK4/6 inhibitors are clinically approved for the treatment of hormone receptor–positive, HER2–negative (HR+/HER2−) breast cancer, but improved specificity and reduced toxicity might expand their use to other indications. Through analysis of publicly available genome-wide loss-of-function data combined with single and dual-targeting CRISPR assays, we found differential cell proliferation vulnerability of cell lines to either CDK4 deletion alone, CDK6 deletion alone, combined CDK4/CDK6 deletion, or neither. CDK6 expression was the best single predictor of CDK4 (negatively correlated) and CDK6 (positively correlated) dependencies in the cancer cell lines, with adenocarcinoma cell lines being more sensitive to CDK4 deletion and hematologic and squamous cancer cell lines being more sensitive to CDK6 deletion. RB–E2F signaling was confirmed as a main downstream node of CDK4/6 in these experiments as shown by the survival effects of RB1 deletion. Finally, we show in a subset of cancer cell lines not dependent on CDK4/6 that CDK2–CCNE1 is an important alternative dependency for cell proliferation. Together, our comprehensive data exploration and functional experiments delineate the landscape of pan-cancer CDK4/6 gene dependencies and define unique cancer cell populations that might be sensitive to CDK4-selective or CDK6-selective inhibitors.

Significance:

This study provides functional genomic insight toward understanding the scenarios in which cancer cells are differentially sensitive to CDK4 or CDK6 inhibition and their implications in current treatment strategies.
Dnmt3a-Mutant Hematopoietic Stem Cell Rewire IFNγ Signaling to Gain Clonal Advantage
Authors: De Dominici Marco , DeGregori James
Published: April 2022

Dnmt3a-mutant stem cells gain a competitive advantage via upregulation of a Txnip–p53–p21 axis and protection from IFNγ induced exhaustion.

See related article by Zhang et al., p. 220 (5).
Practice-Changing Perspectives regarding Systemic Therapy in Early Breast Cancer: Opinions of German Experts regarding the 17th St. Gallen International Consensus Conference
Authors: Kolberg-Liedtke Cornelia , Lüftner Diana , Brucker Sara Y. , Budach Wilfried , Denkert Carsten , Fasching Peter A. , Haidinger Renate , Harbeck Nadia , Huober Jens , Jackisch Christian , Janni Wolfgang , Krug David , Kühn Thorsten , Loibl Sibylle , Müller Volkmar , Schneeweiss Andreas , Thomssen Christoph , Untch Michael , Thill Marc
Published: April 2022

The general topic of this year’s 17th St. Gallen (SG) International Consensus Conference on the treatment of patients with early breast cancer (SG-BCC) was “Customizing local and systemic therapies for women with early breast cancer.” This topic considers that each treatment decision must also consider the cancer-specific situation of the individual patient. This year, the votes of the SG-BCC were again discussed taking into account the multidisciplinary German S3 Guidelines and the recommendations of the Breast Cancer Working Group of the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO Mamma). As the international panel of the SG-BCC consists of experts from different countries, the votes do represent an international cross-section of opinions. Therefore, it is useful to discuss the voting results with respect to the German evidence-based treatment guidelines. This publication focuses mainly on systemic treatment.
Como um estrangeiro entre os homens: existência e temporalidade em Albert Camus
Authors: Rosasco Vitor Urbano
Published: April 2022

Este texto tem como objetivo buscar, nas obras de Camus, uma crítica à experiência contemporânea do tempo: primeiro, retratar e analisar a temporalidade cotidiana que se faz presente em seus textos; em seguida, vislumbrar, nos ensaios e na literatura do autor, possíveis alternativas à rigidez do tempo cotidiano — aquilo que, para os fins do texto, denominaremos suspensão do tempo —; por fim, elaborar uma apreciação das hipóteses camusianas, discutindo seus valores, bem como seus limites. Nesta última parte, em especial, serão utilizados textos de outros autores — no intuito de atualizar e acrescentar novos elementos à problemática camusiana. Entre os autores estão: Debord (pseudonecessidade); Baudrillard (consumo); Woodcock (relógio); Campagna (trabalho e aventura). Tudo isso será feito brevemente, indicando horizontes possíveis — de crítica, mas também de refúgio.
A tirania da maioria segundo J. S. Mill
Authors: Brand Isabel de Almeida
Published: April 2022

O artigo tem como objetivo a discussão dos argumentos contra a tirania da maioria expostos no livro On Liberty (1859) de John Stuart Mill. Primeiramente, investigaremos o princípio de dano, defendido por Mill em seu conceito de liberdade, segundo o qual só se pode interferir na liberdade de qualquer indivíduo para garantir, individual ou coletivamente, a autodefesa. Em seguida, analisaremos a relação desse princípio com a crítica que Mill faz à tirania da maioria. Dessa forma, exploraremos como a imposição da regra da maioria sobre as individualidades é um entrave para o desenvolvimento e a liberdade dos seres humanos. Em suma, pretendemos examinar, a partir do pensamento político de Mill, em que medida a intervenção do governo e da sociedade civil, apoiada na regra da maioria, afeta a liberdade de escolha e de ação dos indivíduos.
O que é "doença"?
Authors: Garbelotto Fellipy Antonio Lopes
Published: April 2022

Este ensaio visa fornecer diferentes compreensões acerca do conceito de “doença” como categorias úteis de avaliação de discursos e estratégias aplicadas durante a pandemia do novo coronavírus. Para isso, é realizada uma exposição histórica da construção de três compreensões distintas do conceito, a saber, as que chamamos de ontológica, dinâmica e fisiológica. A partir dessa distinção, é demonstrada a aplicabilidade avaliativa de uma delas, a ontológica, por meio da
análise crítica de alguns discursos e estratégias de enfrentamento à COVID-19.
Amor fati: delineamentos da afirmação em Nietzsche e Deleuze
Authors: Romão Amanda de Almeida
Published: April 2022

O artigo explora o conceito de amor fati a partir de sua apresentação no aforismo 276 da obra de Friedrich Nietzsche, A gaia ciência (1882), tensionando posteriormente com o uso do conceito na série “Do Acontecimento”, em Lógica do sentido (1969), de Gilles Deleuze. O objetivo será apresentar as diferentes maneiras de afirmar a vida em ambos os filósofos, fazendo aliança com outros dois de seus conceitos, eterno retorno (Nietzsche) e contraefetuação (Deleuze).
Como o SARS-COV-2 virou SARS-COV-2: a trajetória de um objeto científico no início da pandemia no Brasil
Authors: Labate Caio Morello , Borda Pedro
Published: April 2022

Este artigo tem por objetivo tecer reflexões acerca do SARS-COV-2 a partir da ontologia contingente de Bruno Latour, indicando a possibilidade de acompanhar em retrospectiva os passos pelos quais o novo coronavírus foi desenvolvendo capacidade crescente de, agindo, fazer-nos agir. Diante das controvérsias suscitadas pela pandemia, realizou-se um estudo de caso que teve por fontes o depoimento público de especialistas quanto à gravidade da situação e postagens humorísticas na internet (memes) que circularam durante o início do
ano de 2020. Observou-se que, conforme o status do vírus modificava-se através de novas associações tecnocientíficas, houve, respectivamente a cada fonte, robusta mudança de posicionamento e ligeira tendência da ironia à preocupação. Com isso, busca-se mapear a trajetória inicial traçada pelo SARS-COV-2 enquanto um objeto científico, relacionando-se as transformações por ele sofridas em sua potência de agir ao acúmulo e à articulação de fatos científicos gradualmente estabelecidos. Sugere-se, em conclusão, que tais transformações implicam a constante reformulação, sob risco de incoerência, das respostas coletivas ao
vírus.
Pensar as crises com Hannah Arendt: um exercício de pensamento sobre educação, política e pandemia
Authors: Ciochetti Vitor Miranda , Ultramari Nicholas Yoshizato
Published: April 2022

Com a pandemia do novo Coronavírus, a palavra crise tem sido amplamente utilizada no debate público. Nosso objetivo consiste em propor um exercício de pensamento sobre o conceito de crise e seu impacto no campo educacional brasileiro a partir das obras de Hannah Arendt. Se, para a autora, a crise se manifesta no desaparecimento do senso comum, entende-se que, para a educação, seus efeitos consistem na perda do chão de nossas certezas sobre qual o legado que devemos preservar e a quais experiências do mundo podemos recorrer. Por meio de uma investigação do sentido da prática educativa e de acontecimentos da cena política brasileira, apresentamos um contraponto às atuais discursividades pedagógicas em vigor no debate público. Neste sentido, defendemos uma prática educativa marcada por uma temporalidade que não esteja voltada para o futuro, mas para o passado, na qual o objetivo da educação não seja a busca por desenvolver competências para o progresso social, mas a renovação das experiências com o mundo.
Atos cinematográficos em Limite (1931): uma análise deleuziana
Authors: Campos Thiago Borges
Published: April 2022

Este trabalho busca articular o estudo deleuziano acerca dos atos cinematográficos (quadro, decupagem e montagem) com o filme Limite (1931) realizado por Mario Peixoto (1908-1992). A partir de sequências selecionadas, analisaremos a forma como Peixoto dirigiu o filme que é considerado o melhor do cinema nacional. Tal aproximação, entre Gilles Deleuze (1925-1995) e Mario Peixoto, tem como objetivo fornecer ao filme uma nomenclatura estética capaz de justificar o que faz de Limite “uma obra-prima desconhecida”, termo utilizado pelo crítico Georges Sadoul (1904-1967). Posto isto, é importante ressaltar que, a análise está balizada tanto pelo estudo deleuziana da relação entre cinema e filosofia, como pelos escritos deixados por Peixoto a fim de dialogar diretor e filósofo em torno de uma paixão em comum, o cinema.
Reconstrução do conceito de Social lefortiano a partir do político e da ideologia
Authors: Waughan Elizete
Published: April 2022

O advento da Modernidade, segundo Lefort, é marcado pelo enigma da instituição do Social que, finalmente, se revela aos nossos olhos. Essa descontinuidade que marca a História nos convida a perscrutar movimentos de pensamento sobre o real e o irreal. Nesse sentido, não é possível desviar das fantásticas aventuras da alienação e da ideologia que estão longe de compor uma simples irrealidade. Através do olhar crítico de Lefort sobre estas noções, buscamos iluminar a nova maneira de interrogar o real que a Modernidade inaugura, instaurando as formas de sociedades históricas em contraponto às sociedades estagnadas da Pré-modernidade.
A Public Love Affair or a Nasty Game? The Chinese Tabloid Newspaper and the Rise of the Opera Singer as Star
Authors: Yeh Catherine Vance
Published: April 2022

At the end of the nineteenth and beginning of the twentieth century an unlikely new figure emerged on the Chinese national stage to take its place as the new star: the Peking Opera singer and in particular the dan or female impersonator, hitherto a member of the lowest social caste and generally discriminated against by law and social custom. These singers’ newly gained national reputation had everything to do with Shanghai and its media industry, more precisely with the appearance of the tabloids, the xiaobao, in the 1890s. Within a decade, the opera singer had become the selling point of the entertainment newspapers, and very soon newspapers and magazines specialising only in the Peking opera and its stars made their appearance. Propelled by Shanghai’s technologically advanced print entertainment products with their lithograph illustrations and photographs, the image of the star became a national icon and a central figure in the mass media. This paper focuses on three cases in which dan actor(s) were the focus of discussion and at times the object of fierce debate or attacked in the xiaobao. Although different in nature, these events highlighted the changing social position of the actors and of the forms of patronage. The paper analyses the contradictory moral standards applied by the editors and writers of these xiaobao in dealing with the change in the social status of actors; the intersection between traditional private literati patronage of local opera singers and the very public process in which the newspaper made them national stars; and the star actors’ tenuous relationship to the xiaobao with their potential for mass appeal and defamation.
Acquisitive Prescription in Early Modern International Law
Authors: Batson Alexander
Published: April 2022

This article examines the role of Roman acquisitive prescription in early modern international law debates. The ubiquity of prescription demonstrates the importance of Roman private law in the development of international law. Yet, although it was a widely-used juristic concept, there was no consensus about its legitimacy in international relations from 1500 to 1800. Debates raged over whether it was a product of the natural law, the law of nations, or the Roman civil law. There was a crucial tension between prescription’s utility in confirming the political status quo and its tendency to justify ownership based on prior injustice or violence. In assessing the place of prescription in international law, this article examines its use by Grotius, Vázquez, Freitas, Boecler, Conring, Bellarmine, Solórzano, and others in debates over freedom of the seas, imperial possessions in the Americas, Dutch independence, papal temporal power, and the aftermath of the Thirty Years War.
The Astrolabe and the Book in 16th Century France
Authors: Turner Anthony
Published: April 2022

The relationship between books about astrolabes and the instruments themselves is examined through an analysis of the numbers surviving, and something of the context in which they were produced. Such biographical information as is available for the makers of astrolabes in France is rehearsed, and a checklist of surviving instruments is appended.
“To Multiply Corn Two-Hundred-Fold”
Authors: Niermeier-Dohoney Justin
Published: April 2022

Agricultural reform movements proliferated in seventeenth-century Europe. For many who sought to make farming more economically productive, the practices of chymistry offered a way to accomplish these goals. Placed in the context of the development of a “vegetable philosophy,” or a theory of generation and growth across mineralogical and botanical domains, this article examines the application of chymical techniques in the attempt to enhance wheat seeds through seed-steeping and “fructifying” experiments among seventeenth-century agricultural reformers, particularly in England. I focus on three main sources: instructional husbandry manuals describing how to create “fructifying waters” to fertilize these seeds, the writings of Hugh Plat and Francis Bacon detailing their experiments on wheat seed germination, and the manuscript notebooks and correspondences of the Hartlib Circle, a group of natural philosophers, alchemists, and agricultural reformers who attempted to put these ideas into practice in the 1640s and 1650s. Their attempt to develop an artificial fertilizer regime for important cereal crops like wheat played a small but crucial role in the origins of the British Agricultural Revolution in the seventeenth century.
Quintilian on Laughter (Inst. 6.3)
Authors: Loporcaro Laura
Published: April 2022

This paper presents a reading of the chapter on laughter in Quintilian’s Institutio oratoria (Inst. 6.3), the fullest treatise on ancient rhetoric extant. It argues that Inst. 6.3 can be better understood in light of the context of the treatise, and that it can be read as a little mise-en-abyme of, and reversely magnifying lens on, the whole. First, it briefly outlines Quintilian’s two main claims to originality: his aim to educate the ideal orator, who is both technically and morally outstanding, and his thorough, but practical-minded didactic method. Then, it shows how the didactic spin of the treatise can be detected in his discussion of laughter, and how his remarks on the nature of laughter (and the laughable) characterize it as problematic both from a didactic point of view and for the conception of the ideal orator. The difficulties to classify laughter make it hard to teach and control. It is attributed the potential to undermine the very social status and moral character of the orator: it is inexplicable, and potentially dangerous for anyone trying to elicit it. Nevertheless, Quintilian treats laughter as a part of the orator’s rhetorical arsenal, which shows that it is a powerful weapon the benefits of which must outweigh its risks. This raises the question wherein its utility lies exactly, which is addressed in the last section of the paper. Drawing some parallels to modern theories of laughter allows to better understand some dynamics behind laughter in a forensic context that Quintilian only implies. Overall, this paper aims to present a case study on the extent to which the Institutio is an artful and thoroughly thought-through literary construct, and to make a small contribution to recent scholarship on the literariness of ancient didactic prose.
A Glimpse of China’s Earliest Decision-Making: The Meaning of Zhēn 貞 ‘Test’ in the Huāyuánzhuāng East Oracular Inscriptions
Authors: Schwartz Adam Craig
Published: April 2022

Statistics drawn from the Shāng oracle bone inscriptions discovered in Pit H3 at Huāyuánzhuāng East challenge an assumption that all divination statements, or ‘charges’ mìng cí 命辭, be classified as zhēn cí 貞辭, and question an inflexible practice that systematically reads the prefatory word zhēn 貞 ‘test (the correctness of)’ into a divination account when it is absent. The restricted use of zhēn in this unified corpus of inscriptions implies that it had a particular and focused application in the process of decision-making. The Huāyuánzhuāng East inscriptions thus reveal a complex divination matrix that exemplifies the development of royal divination as an institution at Ānyáng more widely.
The new tribe Fourraeeae (Brassicaceae) and two Moroccan Arabis species transferred to the new genus Hurkaea
Authors: KOCH MARCUS A. , KARL ROBERT , AL-SHEHBAZ IHSAN A. , GERMAN DMITRY A.
Published: April 2022

The taxonomic limits of two Moroccan Arabis species are revised based on a critical evaluation of morphology in light of phylogenetic and cytogenetic studies that also included the monospecific European Fourraea. As a result, the new tribe Fourraeeae, the new genus Hurkaea and new combinations H. josiae, H. conringioides, and H. conringioides subsp. humbertii are proposed. Keys to distinguish genera, species and subspecies are provided.
Deep whole-genome resequencing sheds light on the distribution and effect of amphioxus SNPs
Authors: Zhu Yunchi , Lu Na , Chen J.-Y. , He Chunpeng , Huang Zhen , Lu Zuhong
Published: April 2022

Background

Amphioxus is a model organism for vertebrate evolutionary research. The significant contrast between morphological phenotypic similarity and high-level genetic polymorphism among amphioxus populations has aroused scientists' attention. Here we resequenced 21 amphioxus genomes to over 100X depth and mapped them to a haploid reference.

Results

More than 11.5 million common SNPs were detected in the amphioxus population, which mainly affect genes enriched in ion transport, signal transduction and cell adhesion, while protein structure analysis via AlphaFold2 revealed that these SNPs fail to bring effective structural variants.

Conclusions

Our work provides explanation for “amphioxus polymorphism paradox” in a micro view, and generates an enhanced genomic dataset for amphioxus research.
Host cell interactions of novel antigenic membrane proteins of Mycoplasma agalactiae
Authors: Barbosa Maysa Santos , Marques Lucas Miranda , Timenetsky Jorge , Rosengarten Renate , Spergser Joachim , Chopra-Dewasthaly Rohini
Published: April 2022

Background

Mycoplasma agalactiae is the main etiological agent of Contagious Agalactia syndrome of small ruminants notifiable to the World Organization for Animal Health. Despite serious economic losses, successful vaccines are unavailable, largely because its colonization and invasion factors are not well understood. This study evaluates the role of two recently identified antigenic proteins (MAG_1560, MAG_6130) and the cytadhesin P40 in pathogenicity related phenotypes.

Results

Adhesion to HeLa and sheep primary mammary stromal cells (MSC) was evaluated using ELISA, as well as in vitro adhesion assays on monolayer cell cultures. The results demonstrated MAG_6130 as a novel adhesin of M. agalactiae whose capacity to adhere to eukaryotic cells was significantly reduced by specific antiserum. Additionally, these proteins exhibited significant binding to plasminogen and extracellular matrix (ECM) proteins like lactoferrin, fibrinogen and fibronectin, a feature that could potentially support the pathogen in host colonization, tissue migration and immune evasion. Furthermore, these proteins played a detrimental role on the host cell proliferation and viability and were observed to activate pro-apoptotic genes indicating their involvement in cell death when eukaryotic cells were infected with M. agalactiae.

Conclusions

To summarize, the hypothetical protein corresponding to MAG_6130 has not only been assigned novel adhesion functions but together with P40 it is demonstrated for the first time to bind to lactoferrin and ECM proteins thereby playing important roles in host colonization and pathogenicity.
Methodological conduct of prognostic prediction models developed using machine learning in oncology: a systematic review
Authors: Dhiman Paula , Ma Jie , Andaur Navarro Constanza L. , Speich Benjamin , Bullock Garrett , Damen Johanna A. A. , Hooft Lotty , Kirtley Shona , Riley Richard D. , Van Calster Ben , Moons Karel G. M. , Collins Gary S.
Published: April 2022

Background

Describe and evaluate the methodological conduct of prognostic prediction models developed using machine learning methods in oncology.

Methods

We conducted a systematic review in MEDLINE and Embase between 01/01/2019 and 05/09/2019, for studies developing a prognostic prediction model using machine learning methods in oncology. We used the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, Prediction model Risk Of Bias ASsessment Tool (PROBAST) and CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) to assess the methodological conduct of included publications. Results were summarised by modelling type: regression-, non-regression-based and ensemble machine learning models.

Results

Sixty-two publications met inclusion criteria developing 152 models across all publications. Forty-two models were regression-based, 71 were non-regression-based and 39 were ensemble models. A median of 647 individuals (IQR: 203 to 4059) and 195 events (IQR: 38 to 1269) were used for model development, and 553 individuals (IQR: 69 to 3069) and 50 events (IQR: 17.5 to 326.5) for model validation. A higher number of events per predictor was used for developing regression-based models (median: 8, IQR: 7.1 to 23.5), compared to alternative machine learning (median: 3.4, IQR: 1.1 to 19.1) and ensemble models (median: 1.7, IQR: 1.1 to 6). Sample size was rarely justified (n = 5/62; 8%). Some or all continuous predictors were categorised before modelling in 24 studies (39%). 46% (n = 24/62) of models reporting predictor selection before modelling used univariable analyses, and common method across all modelling types. Ten out of 24 models for time-to-event outcomes accounted for censoring (42%). A split sample approach was the most popular method for internal validation (n = 25/62, 40%). Calibration was reported in 11 studies. Less than half of models were reported or made available.

Conclusions

The methodological conduct of machine learning based clinical prediction models is poor. Guidance is urgently needed, with increased awareness and education of minimum prediction modelling standards. Particular focus is needed on sample size estimation, development and validation analysis methods, and ensuring the model is available for independent validation, to improve quality of machine learning based clinical prediction models.
Rebound phenomenon and its risk factors after hemiepiphysiodesis using tension band plate in children with coronal angular deformity
Authors: Choi Kug Jin , Lee Sanghoon , Park Moon Seok , Sung Ki Hyuk
Published: April 2022

Background

This study was performed to evaluate the rebound phenomenon after the correction of coronal angular deformity by hemiepiphysiodesis using tension band plate in children and to identify its risk factors.

Methods

We reviewed 50 children (mean age, 11.0 ± 2.5 years) with 94 physes who had undergone hemiepiphysiodesis using tension band plate due to coronal angular deformity of the lower limb. Patients’ demographic data including sex, age at initial surgery and plate removal, affected bone (distal femur or proximal tibia), affected side, and body mass index were collected. The mechanical lateral distal femoral angle (mLDFA) and the mechanical medial proximal tibial angle (mMPTA) were measured from the teleradiogram, Physes were divided into rebound and non-rebound group, and rebound group was defined as the physes which had  ≥  5° of mLDFA or mMPTA returning to its original deformity. Generalized estimating equation based multivariable analysis was used to identify the risk factors for the rebound phenomenon after the deformity correction.

Results

A total of 41 physes classified into rebound group and 53 physes into non-rebound group. There were significant differences in the age at initial surgery (p = 0.004), the age at implant removal (p = 0.002), the amount of correction (p = 0.001), and the rate of correction (p < 0.001) between two groups. The rate of correction was significantly associated with the rebound phenomenon (p = 0.044). The risk of rebound phenomenon was 1.2-fold higher as the rate of correction increased by 1° per year. The cutoff values of the correction rate between the two groups were 6.9°/year (p < 0.001).

Conclusions

This study showed that the rebound group had younger age and faster correction rate than those in the non-rebound group. In addition, the correction rate for deformity was a significant risk factor for the rebound phenomenon after hemiepiphysiodesis using the tension band plate. Close monitoring after implant removal is required for children who have a rapid correction rate over 7°/year.
Does a suggested diagnosis in a general practitioners’ referral question impact diagnostic reasoning: an experimental study
Authors: Staal J. , Speelman M. , Brand R. , Alsma J. , Zwaan L.
Published: April 2022

Background

Diagnostic errors are a major cause of preventable patient harm. Studies suggest that presenting inaccurate diagnostic suggestions can cause errors in physicians’ diagnostic reasoning processes. It is common practice for general practitioners (GPs) to suggest a diagnosis when referring a patient to secondary care. However, it remains unclear via which underlying processes this practice can impact diagnostic performance. This study therefore examined the effect of a diagnostic suggestion in a GP’s referral letter to the emergency department on the diagnostic performance of medical interns.

Methods

Medical interns diagnosed six clinical cases formatted as GP referral letters in a randomized within-subjects experiment. They diagnosed two referral letters stating a main complaint without a diagnostic suggestion (control), two stating a correct suggestion, and two stating an incorrect suggestion. The referral question and case order were randomized. We analysed the effect of the referral question on interns’ diagnostic accuracy, number of differential diagnoses, confidence, and time taken to diagnose.

Results

Forty-four medical interns participated. Interns considered more diagnoses in their differential without a suggested diagnosis (M = 1.85, SD = 1.09) than with a suggested diagnosis, independent of whether this suggestion was correct (M = 1.52, SD = 0.96, d = 0.32) or incorrect ((M = 1.42, SD = 0.97, d = 0.41), χ2(2) =7.6, p = 0.022). The diagnostic suggestion did not influence diagnostic accuracy (χ2(2) = 1.446, p = 0.486), confidence, (χ2(2) = 0.058, p = 0.971) or time to diagnose (χ2(2) = 3.128, p = 0.209).

Conclusions

A diagnostic suggestion in a GPs referral letter did not influence subsequent diagnostic accuracy, confidence, or time to diagnose for medical interns. However, a correct or incorrect suggestion reduced the number of diagnoses considered. It is important for healthcare providers and teachers to be aware of this phenomenon, as fostering a broad differential could support learning. Future research is necessary to examine whether these findings generalize to other healthcare workers, such as more experienced specialists or triage nurses, whose decisions might affect the diagnostic process later on.

Trial registration

The study protocol was preregistered and is available online at Open Science Framework (https://osf.io/7de5g).
Mammalian tumor-like organs. 2. Mammalian adipose has many tumor features and obesity is a tumor-like process
Authors: Kozlov A. P.
Published: April 2022

Background

In previous publications, the author developed the theory ofcarcino-evo-devo, which predicts that evolutionarily novel organs should recapitulate some features of tumors in their development.

Main text

Mammalian adipose is currently recognized as a multi-depot metabolic and endocrine organ consisting of several adipose tissues. Although lipid-storing cells and proteins are ancient, the adipose organ as a whole is evolutionarily novel to mammals. The adipose expansion has remarkable similarities with the growth of solid tumors. These similarities are the following: (1) The capability to unlimited expansion; (2) Reversible plasticity; (3) Induction of angiogenesis; (4) Chronic inflammation; (5) Remodeling and disfunction; (6) Systemic influence on the organism; (7) Hormone production; (8) Production of miRNAs that influence other tissues; (9) Immunosuppression; (10) DNA damage and resistance to apoptosis; (11) Destructive infiltration in other organs and tissues. These similarities include the majority of “hallmarks of cancer”. In addition, lipomas are the most frequent soft tissue tumors, and similar drugs may be used for the treatment of obesity and cancer by preventing infiltration. This raises the possibility that obesity, at least in part, may represent an oncological problem. The existing similarities between adipose and tumors suggest the possible evolutionary origin of mammalian adipose from some ancestral benign mesenchymal hereditary tumors. Indeed, using a transgenic inducible zebrafish tumor model, we described many genes, which originated in fish and were expressed in fish tumors. Their human orthologsLEP,NOTCH1,SPRY1,PPARG,ID2, andCIDEAacquired functions connected with the adipose organ. They are also involved in tumor development in humans.

Conclusion

If the hypothesis of the evolutionary origin of the adipose organ from the ancestral hereditary tumor is correct, it may open new opportunities to resolve the oncological problem and the problem of the obesity epidemic. New interventions targetingLEP,NOTCH1,SPRY1,PPARG,ID2, andCIDEAgene network, in addition to what already is going on, can be designed for treatment and prevention of both obesity and tumors.
Trial of transcutaneous electrical acupoint stimulation in laryngopharyngeal reflux disease: study protocol for a randomized controlled trial
Authors: Shen Hailong , Han Yanxun , Wu Di , Hu Lihong , Ma Yunxia , Wu Feihu , Tao Ye , Liu Yehai
Published: April 2022

Background

Patients with persistent globus sensation, throat clearing, chronic cough, hoarseness, and other throat symptoms account for a large proportion of patients in ears, nose, and throat clinics. Laryngopharyngeal reflux disease (LPRD) is increasingly valued by otolaryngologists. Transcutaneous electrical acupoint stimulation (TEAS) is possibly a new method for the treatment of LPRD. This trial aims to determine whether TEAS combined with proton pump inhibitor (PPI) is better than PPI alone in the treatment of LPRD.

Methods

This prospective randomized controlled trial will be implemented in a tertiary hospital in China. Seventy patients diagnosed with LPRD will be randomly assigned to the TEAS + PPI group (intervention group) or PPI group (control group), at a ratio of 1:1. In addition to using PPI, the intervention group will receive TEAS at four groups of acupoints, and each group will be treated for 15 min, once for 60 min, five times a week, for 12 weeks, 60 times. The main outcome will be changes in the Reflux Symptom Index scores at 4, 12, and 24 weeks after treatment. The secondary outcomes will include changes in the reflux finding score, Laryngopharyngeal Reflux-Health-related Quality of Life score, and throat pain visual analog scale score.

Discussion

This trial will explore the feasibility of TEAS combined with PPI for the treatment of LPRD and provide potential evidence for its effectiveness and safety. The results of this study will be published in a peer-reviewed journal.

Trial registration

Chinese Clinical Trial Registry ChiCTR2100046755. Registered on May 28, 2021.
The effect of dexmedetomidine on neuroprotection in pediatric cardiac surgery patients: study protocol for a prospective randomized controlled trial
Authors: Ji Sang-Hwan , Kang Pyoyoon , Song In-Sun , Jang Young-Eun , Lee Ji-Hyun , Kim Jin-Tae , Kim Hee-Soo , Kim Eun-Hee
Published: April 2022

Background

Infants undergoing cardiac surgery under cardiopulmonary bypass are vulnerable to postoperative neurodevelopmental delays. Dexmedetomidine has been shown to have protective effects on the heart, kidneys, and brain in animals and adults undergoing cardiac surgery with cardiopulmonary bypass. We hypothesized that dexmedetomidine would have a neuroprotective effect on infants undergoing cardiopulmonary bypass and planned a prospective randomized controlled trial with postoperative neurodevelopment measurements.

Methods

This is a single-center, prospective, double-blinded, randomized controlled trial with 1:1 allocation. A cohort of 160 infants undergoing cardiac surgery with cardiopulmonary bypass will be enrolled. After induction, dexmedetomidine will be infused with a loading dose of 1 μg/kg and a maintenance dose of 0.5 μg/kg/h or the same amount of normal saline will be administered. Upon initiation of cardiopulmonary bypass, an additional dose of dexmedetomidine (0.01 μg/cardiopulmonary priming volume) will be mixed with the cardiopulmonary bypass circuit. The primary outcome will be the proportion of infants who score lower than 85 in any of the cognitive, language, or motor Bayley scales of infant development-III tests 1 year after the surgery. Other feasible outcome measures will include differences in plasma glial fibrillary acidic protein, troponin I, interleukin-6, urinary neutrophil gelatinase-associated lipocalin, and perioperative major adverse events. The results of the Bayley scales of infant development-III test from the study group and the control group will be compared using a chi-squared test under intention-to-treat analysis. A generalized estimating equation will be used to analyze repeated measurements over time.

Discussion

This study will enable us to assess whether the use of dexmedetomidine can alter the early neurodevelopmental outcome in infants undergoing cardiac surgery with cardiopulmonary bypass and also estimate effects of dexmedetomidine on other organs.

Trial registration

ClinicalTrials.gov NCT04484922. Registered on 24 July 2020
Does closed-loop automated oxygen control reduce the duration of mechanical ventilation? A randomised controlled trial in ventilated preterm infants
Authors: Kaltsogianni Ourania , Dassios Theodore , Greenough Anne
Published: April 2022

Background

Many preterm infants require supplemental oxygen in the newborn period but experience frequent fluctuations of their oxygen saturation levels. Intermittent episodes of hypoxia or hyperoxia increase the risk of complications. Compliance with achievement of oxygen saturation targets is variable, and the need for frequent adjustments of the inspired oxygen concentration increases workload.

Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets and reduce both episodes of hypoxia and hyperoxia and the number of manual adjustments. This study investigates whether CLAC compared with manual oxygen control reduces the duration of mechanical ventilation in preterm infants born at less than 31 weeks of gestation.

Methods

This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 70 infants born at less than 31 weeks of gestational age and within 48 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment until successful extubation. The primary outcome is the duration of mechanical ventilation, and secondary outcomes are the percentage of time spent within target oxygen saturation ranges, the time spent in hypoxia or hyperoxia, the number of manual adjustments required, the number of days on oxygen, the incidence of bronchopulmonary dysplasia and the length and cost of neonatal unit stay. The study is performed following informed parental consent and was approved by the Yorkshire and the Humber-Sheffield Research Ethics Committee (protocol version 1.1, 13 July 2021).

Discussion

This trial will investigate the effect of CLAC on the duration of mechanical ventilation, which is an important clinical outcome as prolonged mechanical ventilation is associated with important adverse outcomes, such as bronchopulmonary dysplasia.

Trial registration

ClinicalTrials.Gov NCT05030337. Registered on 17 August 2021
Dynamic nonlinear algebraic models with scale-similarity dynamic procedure for large-eddy simulation of turbulence
Authors: Yuan Zelong , Wang Yunpeng , Xie Chenyue , Wang Jianchun
Published: April 2022

A dynamic nonlinear algebraic model with scale-similarity dynamic procedure (DNAM-SSD) is proposed for subgrid-scale (SGS) stress in large-eddy simulation of turbulence. The model coefficients of the DNAM-SSD model are adaptively calculated through the scale-similarity relation, which greatly simplifies the conventional Germano-identity based dynamic procedure (GID). The a priori study shows that the DNAM-SSD model predicts the SGS stress considerably better than the conventional velocity gradient model (VGM), dynamic Smagorinsky model (DSM), dynamic mixed model (DMM) and DNAM-GID model at a variety of filter widths ranging from inertial to viscous ranges. The correlation coefficients of the SGS stress predicted by the DNAM-SSD model can be larger than 95% with the relative errors lower than 30%. In the a posteriori testings of LES, the DNAM-SSD model outperforms the implicit LES (ILES), DSM, DMM and DNAM-GID models without increasing computational costs, which only takes up half the time of the DNAM-GID model. The DNAM-SSD model accurately predicts plenty of turbulent statistics and instantaneous spatial structures in reasonable agreement with the filtered DNS data. These results indicate that the current DNAM-SSD model is attractive for the development of highly accurate SGS models for LES of turbulence.
Genetic Epilepsy Syndromes
Authors: Myers Kenneth A.
Published: April 2022

PURPOSE OF REVIEW

This article reviews the clinical features, typical EEG findings, treatment, prognosis, and underlying molecular etiologies of the more common genetic epilepsy syndromes. Genetic generalized epilepsy, self-limited focal epilepsy of childhood, self-limited neonatal and infantile epilepsy, select developmental and epileptic encephalopathies, progressive myoclonus epilepsies, sleep-related hypermotor epilepsy, photosensitive occipital lobe epilepsy, and focal epilepsy with auditory features are discussed. Also reviewed are two familial epilepsy syndromes: genetic epilepsy with febrile seizures plus and familial focal epilepsy with variable foci.

RECENT FINDINGS

Recent years have seen considerable advances in our understanding of the genetic factors underlying genetic epilepsy syndromes. New therapies are emerging for some of these conditions; in some cases, these precision medicine approaches may dramatically improve the prognosis.

Many recognizable genetic epilepsy syndromes exist, the identification of which is a crucial skill for neurologists, particularly those who work with children. Proper diagnosis of the electroclinical syndrome allows for appropriate treatment choices and counseling regarding prognosis and possible comorbidities.
Women’s Issues in Epilepsy
Authors: Bui Esther
Published: April 2022

PURPOSE OF REVIEW

Issues pertaining to women with epilepsy have advanced with a better understanding of multidirectional influences among hormones, seizures, and antiseizure medications, as well as pregnancy-related concerns around fertility, seizure destabilization, and antiseizure medication–associated teratogenicity. This article highlights important developments in this field and reviews best practices in the management of women with epilepsy.

RECENT FINDINGS

Important external hormonal influences may impact women with epilepsy particularly in the context of gender-affirming medications, hormonal replacement therapy, and fertility therapies. Fertility for women with epilepsy is influenced by multiple variables; however, in the absence of preexisting fertility issues, epilepsy per se is not associated with significantly impaired fertility. Once women with epilepsy are pregnant, the majority have a stable course. Antiseizure medication use in pregnancy is associated with major congenital malformations 2 to 5 times that of the general population and is highest with high-dose (≥1500 mg or greater total daily) valproate. Carefully considered changes in drug choice and dose may mitigate these risks. Therapeutic drug monitoring plays an important role in pregnancy care, and under expert supervision, women with epilepsy in pregnancy have similar seizure risks as women with epilepsy who are not pregnant. As women with epilepsy age, bone health and menopause may further be impacted by seizures and antiseizure medications.

The care of women with epilepsy is a multifaceted discipline that recognizes the life-long impact of sex and gender influences on epilepsy care.
Diagnosis, Management of, and Return to Play Guidance for Venous Thromboembolism in Athletes
Authors: Brennan Fred H.
Published: April 2022

Venous thromboembolism (VTE) is not rare and is becoming more recognized in our athletic population. This diagnosis can be elusive. A provider must have a high clinical suspicion and use pretest probabilities to order the appropriate studies and accurately diagnose a VTE. Treatment using direct oral anticoagulants for 3 months is recommended in most cases. Gradual return to play can be achieved after treatment is complete. Some athletes, however, may require lifelong anticoagulation. Return to collision sports may be possible using a timed dose strategy if long-term anticoagulation is needed. The management of an athlete with a VTE should include an individualized treatment plan and involve shared decision making with the athlete, team physicians, and hematologic specialists.
Η επίδραση της εφαρμογής παρεμβατικών προγραμμάτων σχεδιασμένα με συμμετοχικές διεργασίες μάθησης στην αλλαγή των γνώσεων των εκπαιδευτικών της πρωτοβάθμιας εκπαίδευσης στην παροχή πρώτων βοηθειών
Authors: Τσάπαλος Γεώργιος
Published: April 2022

Εισαγωγή: Τα παιδικά ατυχήματα αποτελούν ένα μείζον πρόβλημα στη σύγχρονη κοινωνία. Αρκετά από αυτά συμβαίνουν στο σχολικό περιβάλλον. Η πρόληψη και η φροντίδα αποτελούν κύριους στόχους των εκπαιδευτικών στην διαδικασία της ανάπτυξης και της ευεξίας των μαθητών/τριών. Σκοπός: Ο σκοπός της μελέτης είναι η εκμάθηση βασικών γνώσεων και δεξιοτήτων πρώτων βοηθειών καθώς και η απόκτηση ικανοτήτων που θα συντελέσουν στην αλλαγή της συμπεριφοράς και της στάσης των εκπαιδευτικών όταν χρειαστεί να διαχειριστούν έκτακτες καταστάσεις υγείας. Υλικό – Μέθοδος: Πρόκειται για μία ποσοτική τυχαιοποιημένη ελεγχόμενη μελέτη, της οποίας ο πληθυσμός – στόχος αποτελείται από 908 εκπαιδευτικούς, 458 εκ των οποίων (50.4%) απαρτίζουν την ομάδα εκπαιδευτικής παρέμβασης και οι υπόλοιποι 450 (49.6%) την ομάδα ελέγχου. Η εκπαιδευτική μαθησιακή μέθοδος που χρησιμοποιήθηκε είναι σχεδιασμένη με ενεργητικές συμμετοχικές διαδικασίες μάθησης. Για τη συλλογή των δεδομένων που έλαβαν χώρα από το Σεπτέμβριο του 2015 μέχρι τον Μάιο του 2016, χρησιμοποιήθηκε ερωτηματολόγιο δημογραφικών χαρακτηριστικών και αξιολόγησης των γνώσεων πρώτων βοηθειών, στην αρχή και στο τέλος μίας σχολικής χρονιάς. Το στατιστικό πρόγραμμα IBM SPSS 22.0 συνέβαλε στο να μπορέσουν να αναλυθούν τα αποτελέσματα που προέκυψαν. Σχετικά με τις επαναλαμβανόμενες μετρήσεις χρησιμοποιήθηκε η ανάλυση διασποράς για επαναλαμβανόμενες μετρήσεις (repeated measurements ANOVA) προκειμένου να ελεγχθούν εάν υπάρχουν διαφορές στις μετρήσεις τόσο μεταξύ των ομάδων όσο και χρονικά. Αποτελέσματα: Η στατιστική ανάλυση έδειξε στατιστικά σημαντική διαφορά ανάμεσα στις 2 ομάδες (Pearson’s χ2 test, p<0.001‡) . Πριν πραγματοποιηθεί η παρέμβαση παρατηρήθηκε ότι οι βαθμολογίες ήταν παρόμοιες στις δύο ομάδες, ωστόσο έπειτα από την παρέμβαση η βαθμολογία ήταν σημαντικά υψηλότερη στην ομάδα παρέμβασης, καταδεικνύοντας μεγαλύτερο ποσοστό σωστών απαντήσεων στις περισσότερες ερωτήσεις, σε σύγκριση με την ομάδα ελέγχου (Kruskal-Wallis one way ANOVA, p<0.001). Συμπεράσματα: Τα προγράμματα παρέμβασης σχεδιασμένα με συμμετοχικές διεργασίες μάθησης αυξάνουν το επίπεδο των γνώσεων των εκπαιδευτικών στις πρώτες βοήθειες.