bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Abdomen in a 91-Year-Old Male due to Perforated Jejunal Diverticulitis
Authors: Sammartino Francesco , Selvaggio Ivana , Montalto Gioacchino Maria , Pasecinic Carolina , Dhimolea Sirvjo , Krizzuk Dimitri
Published: November 2020

Non-Meckel small intestine diverticular disease is a rare and mostly asymptomatic condition. However, rare cases of acute and emergent complications bear a high mortality rate. We report a case of a 91-year-old male that presented with an acute abdomen due to perforated jejunal diverticulitis. A review of the literature and key points of the condition are depicted. Although jejunal diverticulosis is rare, it must be considered in the differential diagnosis, especially in the elderly with signs of ambiguous abdominal pain and peritonitis.
Intrathyroidal Thymus (Incidentaloma) Mimicking Thyroid Neoplasia in DICER1 Syndrome
Authors: Niedziela Marek , Sabbaghian Nelly , de Kock Leanne , Foulkes William D.
Published: November 2020

Introduction: With the use of ultrasonography for the evaluation of thyroid and nonthyroid neck diseases, the incidental discovery of previously unsuspected thyroid nodules/nonpalpable lesions has increased. Intrathyroidal thymus arises due to aberrant thymic migration during embryogenesis. It is thought to be rare, fulfils the classiccriteria for diagnosis of an incidentaloma and it can be mistaken for a thyroid nodule. Multinodular goiter is the main endocrine manifestation of DICER1 syndrome, a tumor predisposition syndrome. Careful thyroid examination including ultrasound is thus necessary for DICER1 syndrome patients. Case Report: A 4-year-old prepubertal boy was referred to the pediatric endocrinology department following an earlier diagnosis of pleuropulmonary blastoma (PPB) type III, which is a hallmark component of DICER1 syndrome. The patient underwent surgery followed by chemotherapy. Genetic analysis identified a germline DICER1 pathogenic variant (c.2062C>T, p.R688*)in the child and in 5 relatives. A second somatic DICER1 RNase IIIb hotspot mutation(c.5438A>G, p.E1813G) was identified in DNA extracted from the proband’s PPB. He had no goiter on clinical examination, but a heterogenous, well-delineated, avascular, solid and hypoechogenic lesion with pseudomicrocalcifications was observed in the right lobe (4.1 × 3.1 × 2.6 mm), suggestive of thyroid neoplasia. Diagnostic work-up and a 3-year follow-up excluded thyroid neoplasia and confirmed the diagnosis of an intrathyroid benign thymic lesion. Discussion and Conclusion: This case exemplifies that thyroid incidentalomas in DICER1 syndrome patients should be viewed with great suspicion, but that not all thyroid disorders are indeed DICER1-related in these patients.
Prognostic Value of Serum Magnesium in Mortality Risk among Patients on Hemodialysis: A Meta-Analysis of Observational Studies
Authors: Wu Hongwei , Li Qiang , Fan Lijing , Zeng Dewang , Chi Xianggeng , Guan Baozhang , Hu Bo , Lu Yongping , Yun Chen , Krämer Bernhard , Hocher Berthold , Liu Fanna , Yin Lianghong
Published: November 2020

Background: Previous studies have reported that serum magnesium (Mg) deficiency is involved in the development of heart failure, particularly in patients with end-stage kidney disease. The association between serum Mg levels and mortality risk in patients receiving hemodialysis is controversial. We aimed to estimate the prognostic value of serum Mg concentration on all-cause mortality and cardiovascular mortality in patients receiving hemodialysis. Methods: We did a systematic literature search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify eligible studies that reported the prognostic value of serum Mg levels in mortality risk among patients on hemodialysis. We performed a meta-analysis by pooling and analyzing hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We identified 13 observational studies with an overall sample of 42,967 hemodialysis patients. Higher all-cause mortality (adjusted HR 1.58 [95% CI: 1.31–1.91]) and higher cardiovascular mortality (adjusted HR 3.08 [95% CI: 1.27–7.50]) were found in patients with lower serum Mg levels after multivariable adjustment. There was marked heterogeneity (I2 = 79.6%, p < 0.001) that was partly explained by differences in age stratification and study area. In addition, subgroup analysis showed that a serum Mg concentration of ≤1.1 mmol/L might be the vigilant cutoff value. Conclusion: A lower serum Mg level was associated with higher all-cause mortality and cardiovascular mortality in patients receiving hemodialysis.
Peritubular Capillary Oxygen Consumption in Sepsis-Induced AKI: Multi-Parametric Photoacoustic Microscopy
Authors: Poudel Nabin , Zheng Shuqiu , Schinderle Colleen M. , Sun Naidi , Hu Song , Okusa Mark D.
Published: November 2020

Understanding and measuring parameters responsible for the pathogenesis of sepsis-induced AKI (SI-AKI) is critical in developing therapies. Blood flow to the kidney is heterogeneous, partly due to the existence of dynamic networks of capillaries in various regions, responding differentially to oxygen demand in cortex versus medulla. High energy demand regions, especially the outer medulla, are susceptible to hypoxia and subject to damage during SI-AKI. Proximal tubule epithelial cells in the cortex and the outer medulla can also undergo metabolic reprogramming during SI-AKI to maintain basal physiological status and to avoid potential damage. Current data on the assessment of renal hemodynamics and oxygen metabolism during sepsis is limited. Preclinical and clinical studies show changes in renal hemodynamics associated with SI-AKI, and in clinical settings, interventions to manage renal hemodynamics seem to help improve disease outcomes in some cases. Lack of proper tools to assess temporospatial changes in peritubular blood flow and tissue oxygen metabolism is a barrier to our ability to understand microcirculatory dynamics and oxygen consumption and their role in the pathogenesis of SI-AKI. Current tools to assess renal oxygenation are limited in their usability as these cannot perform continuous simultaneous measurement of renal hemodynamics and oxygen metabolism. Multi-parametric photo-acoustic microscopy (PAM) is a new tool that can measure real-time changes in microhemodynamics and oxygen metabolism. Use of multi-parametric PAM in combination with advanced intravital imaging techniques has the potential to understand the contribution of microhemodynamic and tissue oxygenation alterations to SI-AKI.
Níveis diferenciados de governança corporativa e a probabilidade de violação dos covenants financeiros
Authors: Oliveira Willams da Conceição de , Monte-Mor Danilo Soares
Published: November 2020

A governança corporativa e os covenants financeiros exercem papéis complementares no monitoramento das companhias na medida em que reduzem os conflitos de interesse entre as partes envolvidas durante a confecção de contratos de dívida. Esta pesquisa amplia essa discussão ao analisar se as companhias brasileiras de capital aberto listadas nos níveis diferenciados de governança corporativa da B3 apresentam menor probabilidade de violarem os covenants financeiros em uma análise ex-post à firmação dos contratos. A amostra abrangeu firmas brasileiras não financeiras de capital aberto no período de 2010 a 2018, totalizando 1.310 observações em painel desbalanceado para 206 empresas. Os dados foram obtidos junto ao Economatica, site da B³ e construção de base própria a partir de informações de covenants constantes nas notas explicativas das respectivas firmas. Para apuração e análise dos resultados, foi realizado teste de média T Student e análise de regressão logística com efeito fixo de ano. Os resultados apresentam evidências de que as companhias listadas nos níveis diferenciados de governança corporativa da B³ apresentam menor probabilidade de violarem os covenants financeiros do que as demais companhias não listadas nos respectivos níveis. Tal evidência sugere que os níveis da B³ podem ser usados como proxy de governança em contextos contratuais em que existem conflitos de interesses entre as partes envolvidas.
Comparação entre instrumentos de avaliação do equilíbrio em mulheres adultas e idosas da comunidade
Authors: Orcino Juliane Leite , Vieira Martina Estevam Brom , Sousa Hadassa Costa , Moreira Mariana Ferreira , Bueno Guilherme Augusto Santos , Ribeiro Darlan Martins , Formiga Cibelle Kayenne Martins Roberto , Gervásio Flávia Martins
Published: November 2020

Objetivo: Comparar dois instrumentos de avaliação do equilíbrio, BESTest e Baropodometria, em mulheres da comunidade e verificar a influência da idade, comorbidades e visão no equilíbrio. Método: Estudo tranversal, analítico, realizado com mulheres adultas (50 a 64 anos) e idosas (a partir dos 65 anos). O equilíbrio foi avaliado por uma plataforma baropodométrica e com o Balance Evaluation Systems Test (BESTest). Aplicou-se teste T, Anova, Bonferroni e Regressão Linear utilizando o Software SPSS 23.0, adotando-se p<0,05. Resultados: Participaram 156 mulheres sendo 54 adultas (59 anos ± 3,93) e 102 idosas (71 anos ± 4,8). O BESTest verificou que as mulheres adultas apresentaram melhor desempenho (p<0,01) em relação à idosas nas categorias restrições biomecânicas, transições e antecipações, orientação sensorial, estabilidade de marcha e escore total. Houve relação entre o BESTest e o autorrelato de doenças no grupo de idosas nas categorias restrições biomecânicas, transições/antecipações e escore total (p<0,01). A baropodometria identificou alteração do deslocamento latero-lateral com olhos fechados entre os grupos (p=0,01), sendo que, as idosas apresentaram pior desempenho. Todavia, as ferramentas supracitadas apresentaram pouca relação entre si, tendo sua associação variando entre 5 e 11%. Conclusão: O BESTest e a baropometria foram capazes de detectar diferenças entre o equilíbrio de mulheres adultas e idosas, porém apresentam baixa associação entre si. Sugere-se que sejam adotadas como avaliações complementares e não substituíveis na prática clínica do fisioterapeuta.
Adaptação transcultural do Stroke Upper Limb Capacity Scale (SULCS): um instrumento de avaliação da capacidade manual em indivíduos com hemiparesia
Authors: Faria-Fortini Iza , Nunes Ciomara Maria Pérez , Bretas Gabriela dos Santos , Faria Christina Danielli Coelho de Morais , Scianni Aline Alvim , Teixeira-Salmela Luci Fuscaldi
Published: November 2020

Após a ocorrência do Acidente Vascular Encefálico (AVE), é comum a presença de deficiências residuais, com potencial impacto na utilização dos membros superiores (MMSS) na realização de atividades cotidianas, consideradas essenciais para uma vida independente. O Stroke Upper Limb Capacity Scale (SULCS) avalia a função proximal e distal dos membros superiores de indivíduos pós-AVE por meio de 10 itens, hierarquicamente ordenados, que representam tarefas significativas relacionadas às atividades diárias realizadas em ambiente domiciliar. Objetivo: Adaptar transculturalmente o SULCS para uso no Brasil. Método: O processo de adaptação transcultural foi realizado em cinco estágios, seguindo procedimentos padronizados:  tradução inicial, síntese das traduções, retrotradução, comitê de especialistas e aplicação da versão pré-final em 15 indivíduos pós-AVE. Resultados: As versões original e retrotraduzida apresentaram adequada equivalência semântica. O comitê de especialistas adequou a descrição dos itens às regras gramaticais da língua portuguesa. Em um item da escala, foi acrescentada observação sobre a forma de realização da tarefa, para equivalência experimental, e realizada adaptação do material de teste em três itens, para equivalência cultural. Não foram observadas dificuldades de compreensão dos itens no teste da versão pré-final. Conclusão: O SULCS-Brasil apresentou adequadas equivalências semântica, idiomática, cultural e experimental. Os resultados desse estudo viabilizam o uso do SULCS-Brasil como uma ferramenta para avaliação da capacidade dos membros superiores de indivíduos pós-AVE. Estudos futuros são necessários para continuidade do processo de validação da escala, a partir da investigação de outras propriedades de medida, tais como validade de construto e confiabilidade.
Correlação da evolução do estado funcional com o tempo de ventilação mecânica invasiva em pacientes críticos
Authors: Santos Marilucia Reis dos , Guerreiro Caroline Ferreira , Anjos Jorge Luis Motta , Silva Cássio Magalhães da Silva e
Published: November 2020

Pacientes críticos internados na unidade de terapia intensiva (UTI) comumente apresentam declínio do estado funcional, sendo o tempo de permanência na ventilação mecânica invasiva (VMI) o fator de maior importância relacionado ao comprometimento do desempenho físico. Objetivo: Investigar a correlação da evolução do estado funcional entre a admissão e a alta com o tempo de VMI relacionada a mobilidade. Metodo: Trata-se de um estudo observacional, de delineamento transversal, realizado nas UTI's de um hospital da rede pública estadual. Foi aplicado a escala Functional Status Score Intensive Unit Care (FSS-ICU) por ﬁsioterapeutas treinados para avaliação do estado funcional. Para comparação os grupos foram divididos em clínicos e cirúrgicos e utilizado o teste não paramétrico de Mann-Whitney. Para análise da correlação foi utilizado o coeﬁciente de Spearman. Resultados: A amostra foi composta por 30 pacientes com mediana de idade 49,5 [37,0-67,7] anos, sendo a maioria (53%) do sexo masculino, com mediana de tempo de VMI 132,0 [48,0-192,0] horas, mediana de 4,0 [2,0-6,0] do índice de comorbidades de Charlson, predomínio das cirurgias abdominais (75%) e mediana do FSS entre a admissão e a alta de 12, 0 [10,0-30,7]. Veriﬁcou-se uma correlação negativa de moderada a boa entre o FSS da admissão e da alta com o tempo de VMI em horas (r= -0,50 p= 0,005) (r= -0,71 p< 0,001). Conclusão: Existe correlação negativa entre a evolução do estado funcional na admissão e alta com o tempo de VMI em doentes críticos e o perﬁl diagnóstico também pode interferir nesse desfecho.
Imagens da cidade: o cinema, o espaço público e as transformações da vida urbana no Brasil
Authors: Vitorino Nicoly
Published: November 2020

O estudo apresenta um paralelo entre representações cinematográficas do espaço urbano e as relações sociais entre os sujeitos e o espaço no contexto das fronteiras simbólicas do Brasil contemporâneo. As análises partem da abordagem do cinema enquanto fonte histórica e das teorias de Milton Santos sobre globalização e subdesenvolvimento.
Loss of Endogenously Cycling Adult Cardiomyocytes Worsens Myocardial Function
Authors: Bradley Leigh A. , Young Alexander , Li Hongbin , Billcheck Helen O. , Wolf Matthew J.
Published: November 2020

Rationale:

Endogenously cycling adult cardiomyocytes increase after myocardial infarction (MI) but remain scarce and are generally thought not to contribute to myocardial function. However, this broadly held assumption has not been tested, mainly because of the lack of transgenic reporters that restrict Cre expression to adult cardiomyocytes that reenter the cell cycle.

Objective:

We created and validated a new transgenic mouse,
αMHC
(alpha myosin heavy chain)
-MerDreMer-Ki67p-RoxedCre
(denoted
αDKRC
[cardiomyocyte-specific αMHC-MerDreMer-Ki67p-RoxedCre]) that restricts Cre expression to cycling adult cardiomyocytes and uniquely integrates spatial and temporal adult cardiomyocyte cycling events based on the DNA specificities of orthologous Dre and Cre recombinases. We then created
αDKRC::DTA
mice that expressed an inducible diphtheria toxin in adult cycling cardiomyocytes and examined the effects of ablating these endogenously cycling cardiomyocytes on myocardial function after ischemic-reperfusion (I/R) MI.

Methods and Results:

A tandem
αDKRC
transgene was designed, validated in cultured cells, and used to make transgenic mice. The
αDKRC
transgene integrated between
MYH6
and
MYH7
and did not disrupt expression of the surrounding genes. Compared with controls,
αDKRC::RLTG (Rox-Lox-tdTomato-eGFP
) mice treated with Tamoxifen expressed tdTomato+ in cardiomyocytes with rare Bromodeoxyuridine+, eGFP+ cardiomyocytes, consistent with reentry of the cell cycle. We then pretreated
αDKRC::RLTG
mice with Tamoxifen to activate the reporter before sham or reperfusion (I/R) MI surgeries. Compared with Sham surgery, the I/R MI group had increased single and paired eGFP+ (enhanced green fluorescent protein)+ cardiomyocytes predominantly in the border zones (5.8±0.5 versus 3.3±0.3 cardiomyocytes per 10-micron section, N=8–9 mice per group, n=16–24 sections per mouse), indicative of cycled cardiomyocytes. The single to paired eGFP+ cardiomyocyte ratio was ≈9 to 1 (5.2±0.4 single versus 0.6±0.2 paired cardiomyocytes) in the I/R MI group after MI, suggesting that cycling cardiomyocytes were more likely to undergo polyploidy than replication. The ablation of endogenously cycling adult cardiomyocytes in
αDKRC::DTA
(diphtheria) mice caused progressive worsening left ventricular chamber size and function after I/R MI, compared with controls.

Conclusions:

Although scarce, endogenously cycling adult cardiomyocytes contribute to myocardial function after injury, suggesting that these cells may be physiologically relevant.
Memoirs of an Academic Rōnin: Religious Studies and Mentorship in the Age of Post-Truth
Authors: Ambasciano Leonardo
Published: November 2020

The present article offers a selection of recollections about the author’s professional relationship with his mentor during his cursus studiorum as a graduate student and as a Ph.D. candidate. These memories are preceded by a series of critical reflections on the current state of both Religious Studies and the History of Religions, with a comparative focus on the 1960 scientific mandate of the International Association for the History of Religions (IAHR) and the UK institutional conflation of Theology and Religious Studies (TRS) through the lenses of the early and pioneering Italian experience.

Hopefully, these notes will also prompt a much-needed frank conversation on such delicate topics.
Links between Large-Scale Modes of Climate Variability and Synoptic Weather Patterns in the Southern Indian Ocean
Authors: Udy Danielle G. , Vance Tessa R. , Kiem Anthony S. , Holbrook Neil J. , Curran Mark A. J.
Published: November 2020

Weather systems in the southern Indian Ocean (SIO) drive synoptic-scale precipitation variability in East Antarctica and southern Australia. Improved understanding of these dynamical linkages is beneficial to diagnose long-term climate changes from climate proxy records as well as informing regional weather and climate forecasts. Self-organizing maps (SOMs) are used to group daily 500-hPa geopotential height (z500; ERA-Interim) anomalies into nine regional synoptic types based on their dominant patterns over the SIO (30°–75°S, 40°–180°E) from January 1979 to October 2018. The pattern anomalies represented include four meridional, three mixed meridional–zonal, one zonal, and one transitional node. The frequency of the meridional nodes shows limited association with the phase of the southern annular mode (SAM), especially during September–November. The zonal and mixed patterns were nevertheless strongly and significantly correlated with SAM, although the regional synoptic representation of SAM+ conditions was not zonally symmetric and was represented by three separate nodes. We recommend consideration of how different synoptic conditions vary the atmospheric representation of SAM+ in any given season in the SIO. These different types of SAM+ mean a hemispheric index fails to capture the regional variability in surface weather conditions that is primarily driven by the synoptic variability rather than the absolute polarity of the SAM.
On the Correspondence between Seasonal Forecast Biases and Long-Term Climate Biases in Sea Surface Temperature
Authors: Ma Hsi-Yen , Siongco A. Cheska , Klein Stephen A. , Xie Shaocheng , Karspeck Alicia R. , Raeder Kevin , Anderson Jeffrey L. , Lee Jiwoo , Kirtman Ben P. , Merryfield William J. , Murakami Hiroyuki , Tribbia Joseph J.
Published: November 2020

The correspondence between mean sea surface temperature (SST) biases in retrospective seasonal forecasts (hindcasts) and long-term climate simulations from five global climate models is examined to diagnose the degree to which systematic SST biases develop on seasonal time scales. The hindcasts are from the North American Multimodel Ensemble, and the climate simulations are from the Coupled Model Intercomparison Project. The analysis suggests that most robust climatological SST biases begin to form within 6 months of a realistically initialized integration, although the growth rate varies with location, time, and model. In regions with large biases, interannual variability and ensemble spread is much smaller than the climatological bias. Additional ensemble hindcasts of the Community Earth System Model with a different initialization method suggest that initial conditions do matter for the initial bias growth, but the overall global bias patterns are similar after 6 months. A hindcast approach is more suitable to study biases over the tropics and subtropics than over the extratropics because of smaller initial biases and faster bias growth. The rapid emergence of SST biases makes it likely that fast processes with time scales shorter than the seasonal time scales in the atmosphere and upper ocean are responsible for a substantial part of the climatological SST biases. Studying the growth of biases may provide important clues to the causes and ultimately the amelioration of these biases. Further, initialized seasonal hindcasts can profitably be used in the development of high-resolution coupled ocean–atmosphere models.
Social-Contextual Predictors of Early Adolescents’ Responses to Peer Victimization: Introduction to the Special Issue
Authors: Erath Stephen A. , Troop-Gordon Wendy
Published: November 2020

How youth cope with peer victimization affects their psychosocial adjustment. Although coping processes can be facilitated or hindered by the relational context, social-contextual correlates of coping largely have been overlooked in the peer victimization literature. This special issue addresses this gap by bringing together a series of empirical papers that examine the roles of teachers, peers, and parents in youths’ responses to peer victimization. Multiple methodologies and perspectives are presented, providing a rich foundation for future research. We conclude this special issue with a conceptual paper that explores how different kinds of parental responses to peer victimization influence youths’ ability to cope with peer victimization, as well as their psychosocial development more broadly.
The examination, evaluation and comparison of corrosion effect on different metal surface by various crops based biodiesel
Authors: Chourasia Sajan K , Lakdawala Absar M , Patel Rajesh N
Published: November 2020

Biodiesel is relatively higher corrosive compared to Diesel; consequently, the concern of viability is now a foremost issue. The biodiesel is self-oxidative in the environment; thus, its characteristics might be changed as fuel. The current work investigates the behavior of numerous biodiesel corresponding to corrosion when exposed to the surface of metal coupons. A gas chromatography mass spectrometry (GC-MS) was performed on eight biodiesel and a hypothesis was proposed to corroborate the hypothesis; static immersion tests, scanning electron microscopic (SEM) and surface roughness analysis were conducted. The immersion test was conducted for 150 days at ambient temperature conditions; later on, the corrosion rate of metals was examined. Results indicate that the Bronze has a maximum corrosion rate of 0.0674 mpy with Karanja biodiesel, followed by palm biodiesel. The Karanja biodiesel has the highest susceptibility to corrosion with all metals, while the Diesel is found to be the lowest with intermediate values for Rapeseed and Castor.
Lung ultrasound assessment of acute respiratory distress syndrome caused by coronavirus disease 2019: An observational study
Authors: Li Ruiting , Liu Hong , Qi Hong , Yuan Yin , Zou Xiaojing , Huang Haiyan , Wan Jia , Lv Zheng , Ouyang Yaqi , Pan Shangwen , Zhao Xin , Shu Huaqing , Shang You
Published: November 2020

Background:

An outbreak of coronavirus disease 2019 (COVID-19) took place in Wuhan, China, by the end of 2019, and the disease continues to spread all over the world. The number of patients is increasing rapidly, a large number of infected patients is critically ill, and the mortality is high. However, information on COVID-19 patients is limited, and its clinical characteristics have not been fully studied.

Objectives:

To compare the performances of point-of-care lung ultrasound (LUS) and bedside chest X-ray in assessing the condition of COVID-19 patients with acute respiratory distress syndrome (ARDS).

Methods:

This observational study enrolled 42 COVID-19 patients with ARDS who were admitted to the Department of Critical Care Medicine of the Wuhan Union Hospital from February to April 2020. The point-of-care LUS characteristics of the COVID-19 patients with ARDS were summarized, and the performances of LUS and bedside chest X-ray in assessing the patient’s condition were compared.

Results:

Most of the 42 patients were elderly individuals with chronic clinical diseases. The proportion of patients older than 60 years old was 85.7%. All patients were given invasive mechanical ventilation; eight (19.0%) of them received venovenous extracorporeal membrane oxygenation support. LUS has evident advantages in detecting lung consolidation, patchy shadows, and pleural thickening, and pleural line changes in particular. The receiver operating characteristic analysis indicated that the sensitivity, Youden index, and kappa value for detecting COVID-19 patients with ARDS were higher for LUS than the chest X-ray.

Conclusion:

LUS has better diagnostic accuracy and sensitivity in COVID-19 patients with ARDS than the chest X-ray.
Treating Externalizing Behaviors in Toddlers with ASD Traits Using Parent-Child Interaction Therapy for Toddlers: A Case Study
Authors: Cibralic Sara , Kohlhoff Jane , Wallace Nancy , McMahon Catherine , Eapen Valsamma
Published: November 2020

Up to 27% of children with autism spectrum disorder (ASD) experience clinically significant externalizing behavior. Child emotional dysregulation is thought to be one of the main reasons for the manifestation of externalizing behaviors during toddlerhood and has also been associated with insecure and disorganized parent-child attachment relationships. Parent-Child Interaction Therapy for Toddlers (PCIT-T) is an attachment and behavioral based parent training program targeted at children aged 12 to 24 months with externalizing behavior. This study assessed the effectiveness of PCIT-T in reducing child externalizing behavior as well as improving child emotional regulation and the parent-child attachment relationship in a child with moderate-to-severe ASD traits, low intellectual and adaptive functioning, externalizing behaviors within the clinical range, and a disorganized/insecure mother-child attachment relationship. The intervention occurred over a 12-week period and focused on improving positive parenting skills, parent emotional regulation, and child emotional regulation. Treatment progress was tracked using the Child Behavior Checklist Externalizing Behavior subscale, the Deverux Early Childhood Assessment for Toddlers Attachment/Relationship and Self-Regulation subscales, the Dyadic Parent-Child Interaction Coding System, version 4, and the Strange Situation Procedure. Study results provide preliminary support for the use of PCIT-T in reducing externalizing behavior, improving the parent-child attachment relationship and child emotional regulation. These results indicate that PCIT-T can be beneficial for children with ASD traits, however, further research with a larger sample size is needed to strength these findings.
Interplay between media-related perceptions and perceptions of hostility in international conflicts: Results from a study of German and Greek citizens
Authors: Dohle Marco , Kelm Ole , Bernhard Uli , Klein Björn
Published: November 2020

During the European debt crisis, German and Greek media frequently reported on the political conflict between the two countries. This article examines to what extent the media coverage in one country about the other is considered by German and Greek citizens to be hostile (‘hostile media perception’) and influential (‘influence of presumed influence’). Data from a comparative survey in Germany ( n = 492) and Greece ( n = 484) show that news coverage by foreign media on the European debt crisis is perceived by respondents as hostile against their own country and as influential. Moreover, both media-related perceptions are linked with intensified perceptions of hostility, such as assumptions that an individual’s country is not respected in the other country or that the other country’s citizens are demanding that the individual’s country be punished. Based on these results, it is discussed whether media-related perceptions can have a conflict-intensifying effect in international crises.
Myocardial Tissue Characterization By T2 Mapping in Thalassemia Major
Authors: Pepe Alessia , Martini Nicola , Borrello Rita , Positano Vincenzo , Pistoia Laura , Maggio Aurelio , Guerrini Giulia , Sorrentino Francesco , Paci Cristina , Visceglie Domenico , Pedrinelli Roberto , Meloni Antonella
Published: November 2020

Introduction.The presence of iron deposits results in a significant reduction in all magnetic resonance imaging (MRI) relaxation times (T1, T2 and T2*). In the clinical setting the T2* technique is the method of choice for cardiac iron quantification and it has revolutionized the management of patients with hemoglopinopathies.

Purpose.To compare myocardial T2 against T2* in patients with thalassemia major (TM) for myocardial iron characterization.

Methods.133 TM patients (79 females, 38.4±11.3 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered.

T2 and T2* images were acquired, respectively, with multi-echo fast-spin-echo and gradient-echo sequences. Global heart T2 and T2* values were obtained by averaging the values in all 16 myocardial segments.

The normal T2 range was established as mean±2 standard deviations on data acquired on 80 healthy volunteers (males: 48-56 ms and females: 50-57 ms). The lower limit of normal for global heart T2*, established on the same healthy population, was 32 ms.

Results.A significant correlation was detected between global heart T2 and T2* values (R=0.577; P<0.0001) (Figure).

Out of the 113 (84.9%) patients with a normal global heart T2* value, none had a decreased global heart T2 value, while 58 (51.3%) had an increased T2 value.

Out of the 20 patents with a decreased global heart T2* value, only 10 (50%) had also a reduced T2 value. Conversely, 9 (45.0%) had a normal global heart T2 value and one (4.5) showed an increased T2 value.

The 59 patients with increased global heart T2 value were significantly older than the remaining patients (40.8±10.5 vs 36.4±11.6 years; P=0.019)

Conclusion.All patients with decreased T2 value had also a decreased T2* value and in half of the patients iron load was undetected by T2, suggesting that T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment. However, more than half of TM patients had an increased T2 value, thus may be caused by the presence of myocardial inflammation and/or edema. So, T2 mapping could reveal subclinical myocardial involvement in TM patients.

Figure

Disclosures

Pistoia: Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.
Frequency and Stimulation of NPM1-Specific Immune Responses By Anti-PD1 Antibodies in NPM1-Mutated AML
Authors: Greiner Jochen , Schneider Vanessa , Schrezenmeier Hubert , Wiesneth Markus , Hofmann Susanne , Götz Marlies
Published: November 2020

Nucelophosmin1 (NPM1) is one of the most commonly mutated genes in AML, represents a distinct entity according to the WHO and is commonly associated with a favorable prognosis. We described specific immune responses against immunogenic epitopes derived from the mutational region of NPM1 in AML and specific immune responses against leukemic progenitor and stem cells (LPC/LSC). Immune responses play an increasing role in AML treatment options. However, the role of Immuncheckpoint inhibition is still controversially discussed in AML.

In this work, we investigated NPM1 specific immune responses but also responses against other leukemia associated antigens (LAA) like PRAME (P300), Wilms' Tumor 1 (WT1) and RHAMM (R3) in an extended cohort. We investigated these immune responses in LSC/LPC using colony-forming immunoassays (CFI) and ELISpots. We examine whether immuncheckpoint inhibition using the anti-programmed death 1 (anti-PD-1) antibody might increase immune responses against stem cell like cells, comparing NPM1-mutated (NPM1mut) to NPM1 wildtype (NPM1wt) patients.

In AML NPM1mut patients, specific immune responses of cytotoxic T cells against the epitope NPM1 showed a mean reduction of colonies in CFI of 27%, for P300 of 38%, for WT1 of 32% and for R3 of 42%. NPM1wt patients showed a mean reduction of colonies in CFI of for P300 of 28%, for WT1 of 28% and for R3 of 41%. Results are comparable, for NPM1mut and NPM1wt patients, there were immune responses seen in all epitopes.

When adding the anti-PD-1 antibody to CFI, in NPM1mut patients the mean additional inhibition using NPM1 as target was 47%, and for the other epitopes: P300 23%, WT1 27% and R3 26%. For NPM1WT patients, the additional inhibition with the addition of anti-PD-1 to CFI was for P300 25%, for WT1 34% and for R3 23%.

For the NPM1 epitope, 8 of 10 NPM1mut patients showed an immune response and 3/10 showed reduction in CFI of > 50%. The NPM1 epitope displayed an additional reduction with anit-PD-1 in all 10 NPM1mut Patients and in 6 of 10 a reduction of > 50%. Thus, especially the NPM1 specific immune responses are strong in NPM1mut patients by adding anti-PD-1.

Taken together, the anti-PD-1 antibody increases specific T cell responses of LAA-stimulated CTL and the cytotoxic effect of T cells against LPC/LSC. The effect was strongest in NPM1mut patients against the immunogenic epitope derived from the mutational region of NPM1 and even stronger when adding anti-PD-1. These data suggest there could be a NPM1 mutation directed immunotherapeutic approach using LAA-directed vaccination strategies in NPM1-mutated AML and combination with anti-PD-1 antibodies might open new application possibilities.

Disclosures

Greiner: BMS: Research Funding. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding.
Detection of Myeloid and Clonal Expansion Related Gene Mutations By Whole-Exome Sequencing in Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Chen Fangfei , Han Bing , Li Jian
Published: November 2020

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease presented with hemolysis, cytopenia and thrombosis. Apart from PIGA gene on hematopoietic stem cells which accounts for the glycosylphosphatidylinositol (GPI) anchor deficiency on the cell membrane, other mutations have also been detected in PNH through whole-exome sequencing (WES). However, the characteristics of mutations in patients with PNH and genes which may contribute to PNH clonal expansion have not been well defined.

Methods: Peripheral blood samples were collected from 41 patients with PNH, among them samples from 6 patients were further separated into CD59- and CD59+ fractions by CD59 magnetic beads. Gene mutations were tested by whole-exome sequencing(WES). 178 genes commonly mutated in myeloid cancer were analyzed in the sequencing results, as well as their correlation with clinical indicators. Mutated genes correlated with cell proliferation were compared between sorted CD59+ and CD59- cells.

Results: The most frequently mutated myeloid cancer-related genes were MAP3K4 and CSMD1 (12.2% respectively). Among them, RUNX1T1 mutation was found to be correlated with larger clone size, higher level of uncombined bilirubin, and lower level of hemoglobin (P<0.05). No other correlation between clinical parameters and gene mutations were found. The proportion of mutations (DNMT3A、RUNX1、JAK2、JAK3、CSMD1) which have been shown to indicate poor outcome in patients with aplastic anemia decreased as PNH clone increased (p=0.026). Mutations related to cell proliferation tended to happen more frequently in CD59- fractions compared with CD59+ fractions of the same patient (P=0.062).

Conclusions: Myeloid cancer-related mutations can be detected in patients with PNH with some correlation with clinical manifestations. Larger PNH clone may "save" patients from mutation indicating poor prognosis. CD59- fractions seemed to carry more proliferation related mutations, which may contribute to PNH clonal expansion.

Disclosures

No relevant conflicts of interest to declare.
Case Reports of Treating Abdominal Necrotizing Fasciitis Wit Platelet Rich Plasma
Authors: Wang Shujun , Chen Baoan
Published: November 2020

ObjectivePRP(platelet rich plasma) promotes wound healing by various growth factors including VEGF, TGF-β, PDGF and EGF, all those growth factors are released by activated platelets.

MethodsPRP is applied externally to the necrotizing fasciitis wound after activated with 10% calcium gluconate, then with dressing fixed. PRP is used once a day after the wound is cleaned. The wound area is measured once, wound tissue type and drainage is recorded. Granulation area and percentage are calculated.

ResultsThe case one patient underwent negative pressure drainage treatment before the treatment of PRP. The wound area was 49.41cm2, involving the entire skin layer, with little fluid exudation. The skin around the wound was dry and curving. After 6 times of PRP treatment, the wound was reduced to 15.4cm2 without exudation, and the tissue type was fresh granulation, with 100% granulation proportion. The wound was kept clean after discharge, and reduced to 1.25cm2 after 1 month without special treatment. The wound was fully healed after 2 months, and there was no wound or rupture after the follow up visit of 12 months. The case two patient underwent negative pressure drainage treatment on the wound surface. The wound area was 106.25cm2 and the depth was 1.0cm. The whole skin was involved with stealth. After 21 times of PRP treatment, the wound was reduced to 64.35cm2, and the tissue type was carrion + granulation, which accounted for 85.73%. After autologous skin graft, 100% survived, and the wound was followed up without rupture 10 months later.

ConclusionPRP is a safe and effective method for the treatment of necrotizing fasciitis and promotes wound healing through the release of various growth factors by α-particles in activated platelets. PRP provides a new and effective treatment method for the treatment of necrotizing fasciitis by creating conditions for skin graft, shortening the length of hospital stay, and even eliminating the need for skin graft treatment for some wounds.

Key words: PRP, necrotizing fasciitis, wound

Disclosures

No relevant conflicts of interest to declare.
The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients
Authors: Gui Lin , Wang Fei , Shi Jinning , Chen Baoan
Published: November 2020

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR<3.61) or high NLR group (NLR≥3.61), low MLR group (MLR<0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR< 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB<100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB<100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis.

Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR

Disclosures

No relevant conflicts of interest to declare.
Peripheral Blood Progenitor Cell Mobilization of CD34+ Cells with Combine G-CSF and GM-CSF in Pediatric Patient Outcome and Economic Advantage
Authors: Garcia Heidy lyz
Published: November 2020

Background: Clinical trials to mobilize PBPC for autologous and allogeneic harvesting prior to high dose chemotherapy/radiotherapy include chemotherapy, cytokines, or chemotherapy combine with cytokines. PBPC mobilized by G-CSF or GM-CSF reduces the hematological toxicity and supportive care requirements in recipients of autologous and allogeneic transplants, in our study we combined G-CSF and GM-CSF to mobilize PBPC for transplantation.

Methods: We selected 63 patients with different cancers to participate in the study and 7 healthy donors. We utilize to mobilize in all the patient the combination of G-CSF and GM-CSF (10μg/Kg/day each) administered for 5 consecutive days. Then we proceed it to harvest the PBPC until we obtain a threshold of 2.0 x 10^6/Kg CD34+ cells. A total of 31 PBPC transplants were performed (27 autologous and 8 allogeneic). Neutrophil engraftment was defined as ANC> 500/mm³ and, platelet engraftment was defined as a platelet count > 30,000/mm³ (transfusion independent) for more than 48 hours.

Results: Data on PBC 24, 48, 72, and 96hrs. For the 31 PBPC autologous transplant patients, the median days to ANC>500 was 10.6 days; 11 days for the allogeneic. None of the subject's experience bone pain, headache, flu like side effects or a documented or proven infection. Median days to platelet engraftment following infusion CD34+ cells, was 13.2 for the autologous PBPC; 13 days for the allogeneic.

Conclusions: The combination the G-CSF and GM-CSF (10μg/kg/day x 5 days) was well tolerated. We can appreciate that there is a reduction in the duration and severity of neutropenia as well of thrombocytopenia in both types of transplant (autologous/allogeneic). The GVHD incidence were not increase by the use of G-CSF and GM-CSF. We conclude that this procedure is cost effective and a suitable way to mobilize an average number of PBPC (from 1-3 apheresis) in a shorter amount of time indicating an economic advantage. It is proven to be less expensive than other agent used to mobilize stems cells for transplant.

Disclosures

No relevant conflicts of interest to declare.
Influencing Factors of Non-Genetic Factors Influencing the Overall Survival of Multiple Myeloma Patients
Authors: Gui Lin , Wang Fei , Shi Jinning , Chen Baoan
Published: November 2020

Objective: To explore the non-genetic prognostic factors in patients with multiple myeloma (MM).

Methods: Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters of 51 MM patients who were newly diagnosed with MM and had complete follow-up data in the Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University, Nanjing From November 2011 to October 2012.

Results: Of the 51 patients, 29 were male and 22 were female. Followed up to December 2019, 21 died and 30 survived. The univariate analysis showed the prognosis was influenced by factors including age, disease stage, standard treatment, new drugs, maintenance treatment, hypercalcemia, globulin, albumin, hemoglobin. Patients aged <65 years, with ISS stage I and II, with standardized treatment, with new drugs, with normal or below normal blood calcium, with normal or below normal globulin, with albumin ≥ 35g/L or patients with hemoglobin ≥100g/L have longer survival time. The multivariate analysis showed that maintenance treatment, hypercalcemia and hemoglobin were independent risk factors influencing the prognosis of MM patients.

Conclusion: Patients with blood calcium ≥ 2.6mmol/L, hemoglobin <100g/L and those who do not undergo regular maintenance therapy have a poor prognosis.

Key words multiple myeloma; overall survival; non-genetic; prognostic factors

Disclosures

No relevant conflicts of interest to declare.
IL-6 Deficiency Reverses Leukemic Transformation in an MDS Mouse Model
Authors: Mei Yang , Liu Yijie , Han Xu , Yang Jing , Ji Peng
Published: November 2020

Myelodysplastic syndromes (MDS) are a group of age-related myeloid malignancies that are characterized by ineffective hematopoiesis and increased incidence of developing acute myeloid leukemia (AML). The mechanisms of MDS to AML transformation are poorly understood, which is partially due to the scarcity of leukemia transformation mouse models. Recently, we established a mDia1/miR146a double knockout (DKO) mouse model mimicking human del(5q) MDS. DKO mice present with pancytopenia with aging due to myeloid suppressive cell (MDSC) expansion and over-secretion of pro-inflammatory cytokines including TNF-a and interlukine-6 (IL-6). In the current study, we found that most of the DKO mice underwent leukemic transformation at 12-14 months of age. The bone marrow of these mice was largely replaced by c-Kit+ blasts in a background of fibrosis. Flow cytometry analysis and in vitro colony formation assay demonstrated that hematopoietic stem progenitor cells (HSPCs) in DKO bone marrow were dramatically declined. The leukemic DKO mice had elevated white blood cell counts and circulating blasts, which contributes to the myeloid cell infiltration in non-hematopoietic organs including liver and lung. Moreover, the splenocytes from DKO old mice efficiently reconstitute the hematopoiesis, but led to a 100% disease occurrence with rapid lethality in gramma irradiated recipient mice, suggesting the leukemic stem cells enriched in DKO spleen were transplantable. Given the significant roles of the inflammatory cytokines in the pathogenesis of the DKO mice, we crossed DKO mice with IL-6 knockout mice and generated mDia1/miR-146a/IL-6 triple knockout (TKO) mice. Strikingly, the TKO mice showed dramatic rescue of the leukemic transformation of the DKO mice in that all the aforementioned leukemic phenotypes were abolished. In addition, IL-6 deficiency normalized the cell comparts and prevented leukemic transplantation ability in TKO spleen. Single cell RNA sequencing analyses indicated that DKO leukemic mice had increased monocytic blast population with upregulation of Fn1, Csf1r, and Lgals1, that was completely diminished with IL-6 knockout. Through a multiplex ELISA, we found IL-6 deficiency attenuated the levels of multiple inflammatory cytokines in TKO serum. In summary, we report a mouse model with MDS leukemic transformation during aging, which could be reverted with the depletion of IL-6. Our data indicate that IL-6 could be a potential target in high risk MDS.

Disclosures

No relevant conflicts of interest to declare.