bluuebunny/crossref_metadata_2025 huggingface dataset:
Projeto de extensão voltado a educação em saúde para pacientes com síndrome metabólica pós-infecção de Covid-19 na região Amazônica
Authors: Porfírio Danillo Monteiro , Silva Isabella Mesquita Sfair , Oliva Thirza Damasceno Ramos , Medeiros Janine Maria Rodrigues , Caldeira Gisele Alves Morikawa , Castro Alline Peralta , Kato Beatriz de Souza , Silva Paulo Henrique Monteiro da , Libonati Rosana Maria Feio
Published: December 2023

Em 2020, um novo coronavírus acarretou a declaração pela Organização Mundial da Saúde (OMS) de um evento pandêmico global. Com a expansão da pandemia para mais territórios, o acometimento dos grupos de risco passou a ser significativamente mais evidente do que em grupos previamente hígidos. Indivíduos categorizados como obesos, pacientes diagnosticados com Diabetes Mellitus tipo 2 (DM2) e hipertensos demonstraram ser mais suscetíveis a casos mais graves do que outras parcelas da sociedade, reforçando ainda mais a grande prevalência dessas doenças no mundo moderno. Pelo período curto desde o início dos casos de COVID-19, poucos estudos conseguem abordar o diagnóstico ou mesmo o desenvolvimento das sequelas a longo prazo, o que muitas vezes pode levar anos até serem percebidas ou iniciarem seu curso clínico. Com estudos apontando a possibilidade da ocorrência de sintomas ou agravamento da síndrome metabólica em pacientes pós-infectados, o processo de educação em saúde objetivou estabelecer formas de criar e conscientizar sobre como manter a qualidade de vida e a alimentação saudável, a fim de contribuir para a redução nos impactos negativos a longo prazo da síndrome metabólica prévia ou iniciada após a COVID-19. O projeto de extensão focou, assim, na prevenção do desenvolvimentoa posteriori de complicações ocasionadas pela infecção do SARS-Cov-2 por meio do incentivo a um estilo de vida de qualidade. O uso de cartilhas educativas e questionários de satisfação ao atendimento foram ferramentas para o esclarecimento sobre como realizar as mudanças no estilo de vida, além da atenção multidisciplinar como auxílio na consolidação da educação em saúde para estes pacientes. Desta maneira, os integrantes deste projeto buscaram fomentar a pesquisa sobre esta área ainda com poucos estudos populacionais, incentivando a construção de conhecimento sobre o curso clínico deste vírus. Havendo o contato entre os membros do projeto e os pacientes, a construção das relações ocorre bilateralmente, com a intercomunicação entre o conhecimento acadêmico e os valores culturais, trazendo a melhoria futura para os pacientes.
Atendimento fonoaudiológico à população transgênera: um relato de experiência
Authors: Leal Gilberto da Cruz , Silva Andreá Gracindo da , Silva João Paulo Ferreira da , Martins Melissa França Lima , Sanchez Julia Fonsi , Prudêncio Jonathan Leonardo Gonçalves , Wolf Aline Epiphanio
Published: December 2023

Voz incompatível com a própria identidade é um tema frequentemente apontado pela população transgênera em atendimentos fonoaudiológicos. A fonoterapia é uma técnica que permite a adequação da voz do falante, dentro de um campo de possibilidades. Ao fonoaudiólogo cabe o treinamento, a orientação e o aconselhamento dessa população, levando em conta as especificidades de cada indivíduo. Diante disso, este estudo tem como objetivo relatar a experiência de estudantes de graduação e profissionais de Fonoaudiologia no atendimento voltado à população transgênera em um laboratório de comunicação. Inicialmente são apresentados conceitos-chave, tais como asdiferenças entre sexo, gênero, identidade de gênero, e orientação sexual. São abordados temas como a violência sofrida pela população trans, a busca pela adequação vocal, a criação e o desenvolvimento do ambulatório de comunicação, o acolhimento e o suporte prestado pelos profissionais à população trans e a seus familiares, além dos procedimentos adotados pelo ambulatório. Dentre as conclusões, destaca-se que a assistência fonoaudiológica temmostrado a importância do cuidado centrado no indivíduo, legitimando a garantia da promoção de saúde dos usuários. Ademais, é destacada a importância do profissional de fonoaudiologia no aprimoramento vocal e comunicativo dessa população que é frequentemente estigmatizada.
Avaliação de alterações em tomografia computadorizada de tórax de pacientes internados por Covid-19
Authors: Targino Hugo Alexandre Sousa , Sousa Pedro Henrique Borges , Almeida Caique Marques de , Leite Maria Socorro Lira , Maia Júnior José Roberto , Duarte Andrezza Araújo de Oliveira
Published: December 2023

Introdução: O SARS-CoV-2 possui rápida disseminação e alta infectividade, podendo evoluir com Síndrome da Angústia Respiratória Grave (SARS), o que levou a um número elevado de mortes e internações na recente pandemia. A Tomografia Computadorizada (TC) de tórax demonstrou um papel essencial na avaliação inicial e evolução dessespacientes. Metodologia: Este foi um estudo observacional retrospectivo em centro único - Hospital Universitário no Nordeste do Brasil - avaliando 97 pacientes internados por COVID-19 com confirmação laboratorial, a fim de avaliar e quantificar os achados de TC de tórax, comparando os achados com a gravidade do caso e relacionando-os com as morbidades apresentadas. As TCs foram laudadas por radiologistas do próprio hospital. Após isso, os dados foram avaliados pelo laboratório de estatística da universidade para serem analisados e discutidos. Resultados: Dentre as principais alterações, o vidro fosco estava presente em mais de 90% dos pacientes. Foi observado que a magnitudedo comprometimento pulmonar deste achado apresentou relação desfavorável com o desfecho da internação. Conclusão: Neste sentido, observa-se a relevância da TC de tórax para sugerir o diagnóstico de Covid-19 e estabelecer o prognóstico da doença. No entanto, ainda são necessários mais estudos para destrinchar estes achados.
O destino da literatura
Authors: Barreto Lima
Published: December 2023

Texto por Lima Barreto.
Lima Barreto na sala de aula e na crítica de Osman Lins
Authors: Nitrini Sandra
Published: December 2023

Artigo de teor informativo sobre a presença de Lima Barreto nas aulas de Literatura Brasileira, proferidas por Osman Lins na antiga Faculdade de Filosofia, Ciências e Letras de Marília (SP), de 1970 a 1976. Nas anotações preparatórias para essas aulas e aquelas dedicadas a elementos da narrativa, em especial ao espaço, encontra-se o embrião de sua tese de doutorado, Lima Barreto e o espaço romanesco. Como professor e como crítico, Osman Lins contribuiu para recolocar o esquecido Lima Barreto em circulação literária na década de 1970 e valorizar sua obra.
Estratégias para Promover a Adaptação de Alunos Ingressantes à Universidade, no Ensino Remoto Emergencial: Oficinas de Autorregulação da Aprendizagem e Plataforma Online Lt-kuraCloud
Authors: Casale Karina Reche , Bettioli Ana Luisa , Santos Daniel Araújo da Silva , Graciola Marilda Aparecida Dantas , Pelissoni Adriane S. M. , Consoni Juliana Barbosa , Marcondes Fernanda Klein
Published: December 2023

Durante o primeiro ano na universidade, muitos estudantes enfrentam desafios para se adaptar devido à falta de hábitos diários de estudo e habilidades para lidar com as novas demandas acadêmicas, pessoais e econômicas. A pandemia de COVID-19 introduziu obstáculos adicionais com o ensino remoto emergencial. Para auxiliar os estudantes de Odontologia ingressantes na Universidade Estadual de Campinas, Piracicaba – SP, Brasil, o Serviço de Apoio ao Estudante foi solicitado a implementar workshops de aprendizagem autorregulada online, anteriormente realizados presencialmente. Além disso, lições interativas na plataforma Lt-kuraCloud foram usadas como recurso suplementar em atividades assíncronas. Este estudo, aprovado pelo Comitê de Ética da FOP, buscou avaliar as percepções dos estudantes sobre essas estratégias. Os workshops abordaram 4 tópicos: adaptação à vida universitária, definição de metas acadêmicas, técnicas de estudo e gerenciamento de tempo. As lições interativas na plataforma Lt-Kuracloud apresentavam textos explicativos, vídeos e exercícios com feedback imediato, oferecendo uma alternativa de estudo e avaliação formativa, como atividade assíncrona. Ao final do primeiro semestre de 2020, 66 estudantes avaliaram a utilidade dos workshops e das lições online em uma escala de 1 a 5, sendo 1 não útil. Suas médias foram 3,83 ± 0,99 para os workshops e 4,76 ± 0,50 para as lições. De acordo com os estudantes, os workshops auxiliaram na organização dos estudos, no controle socioemocional e na socialização acadêmica. Eles também relataram que as lições online melhoraram a compreensão, retenção e aplicação do conhecimento. Em resumo, os estudantes consideraram essas estratégias benéficas para sua experiência de aprendizado.
Mental disorders in judicial workers: analysis of sickness absence in a cohort study
Authors: Melo Bruna Ferreira
Published: December 2023

In the article “Mental disorders in judicial workers: analysis of sickness absence in a cohort study”, https://doi.org/10.11606/s1518-8787.2023057004737, published on the Revista de Saúde Pública.2023;57:72, the RSP corrects on page 1 the authorship order and how to cite, and on page 10 the authors’ contributions.
On page 1
Where it reads: Bruna Ferreira MeloI, Kionna Oliveira Bernardes SantosI, Rita de Cássia Pereira FernandesI, Verônica Maria Cadena de LimaI, Susan StockII
It should read: Bruna Ferreira MeloI, Kionna Oliveira Bernardes SantosI, Susan StockII, Verônica Maria Cadena de LimaI, Rita de Cássia Pereira FernandesI
Where it reads:
How to cite: Melo BF, Santos KOB, Fernandes RCP, Lima VMC, Stock S. Mental disorders in judicial workers: analysis of sickness absence in a cohort study. Rev Saude Publica. 2023;57:72. https://doi.org/10.11606/s15188787.2023057004737
It should read:
How to cite: Melo BF, Santos KOB, Stock S, Lima VMC, Fernandes RCP. Mental disorders in judicial workers: analysis of sickness absence in a cohort study. Rev Saude Publica. 2023;57:72. https://doi.org/10.11606/s15188787.2023057004737
On page 10
Where it reads:
Authors’ Contribution: Study design and planning: KOB; RCP. Data collection, analysis, and interpretation: BFM; VMCL; KOB. Manuscript drafting or review: BFM; KOB; RCP. Approval of the final version: KOB; RCP; SS. Public responsibility for the content of the article: BFM; KOB.
It should read:
Authors’ Contribution: Study design and planning: KOB; RCP. Data collection, analysis and interpretation: BFM; VMCL; KOB; RCP; SS. Manuscript drafting or review: BFM; KOB; RCP; SS. Approval of the final version: BFM; KOB; RCP; SS. Public responsibility for the content of the article: BFM; KOB.
Mental disorders in judicial workers: analysis of sickness absence in a cohort study
Authors: Melo Bruna Ferreira , Santos Kionna Oliveira Bernardes , Fernandes Rita de Cássia Pereira , Lima Verônica Maria Cadena de , Stock Susan
Published: December 2023

OBJECTIVE: To analyze risk factors for sickness absence due to mental disorders among judicial workers in Bahia, Brazil. METHODS: Retrospective cohort with follow-up from 2011 to 2016 with 2,660 workers of a judicial sector in Bahia, Brazil. The main outcome measures were survival curves estimated for the independent variables using the Kaplan-Meier product limit estimator and risk factors for the first episode of sickness absence calculated based on the Cox regression model. RESULTS: The survival estimate of the population of this study for the event was 0.90 and from the Cox model the risk factors for the first episode of sickness absence due to mental disorders were: female (HR = 1.81), occupation of magistrate (HR = 1.80), and age over 30 years old (HR = 1.84). In addition, the risk for new cases of sickness absence among women reached 4.0 times the risk for men, in 2015. The estimated relative risks of sickness absence and the observed survival reduction behavior over time add information to the literature on sociodemographic and occupational factors associated with sickness absence due to mental disorders in the public sector. CONCLUSION: These results highlight the need for further research to more precisely identify vulnerable groups at risk of preventable mental health-related sickness absence in the workplace, better identify the workplace organizational factors that contribute to these disorders as well as studies on the effectiveness of workplace interventions to improve mental health among judicial and other public sectors workers.
Programa Maior Cuidado diante dos desafios do envelhecimento: uma análise qualitativa
Authors: Castro Cláudio Phillipe Fernandes de , Aredes Janaína de Souza , Giacomin Karla Cristina , Firmo Josélia Oliveira Araújo
Published: December 2023

OBJETIVO: Compreender a percepção de diferentes atores envolvidos no processo de cuidado ao idoso na estratégia intersetorial do Programa Maior Cuidado (PMC), visando o desenvolvimento de ações que contribuam para a melhoria dos serviços prestados. MÉTODOS: Foram realizadas 11 entrevistas qualitativas guiadas por roteiro semiestruturado em 2020 junto a informantes-chave diretamente envolvidos no PMC: idosos e seus familiares, cuidadores, profissionais da saúde e da assistência social. Adicionalmente, com o objetivo de compreensão do funcionamento e das propostas do PMC, também foi realizada uma análise documental com o rastreamento de informações existentes sobre as diretrizes, os protocolos e os instrumentos de gestão. Utilizou-se a técnica de análise de conteúdo para classificar os dados textuais, e o processo de interpretação foi mediado pelo referencial teórico-metodológico da antropologia hermenêutica. RESULTADOS: Foram identificadas duas categorias: “Repercussões do cuidado ofertado pelo PMC: o ‘pouco’ que faz diferença” e “Problemas para além do PMC: os limites do cuidado familiar diante da violência contra a pessoa idosa”. Para todos os entrevistados é uníssona a percepção de que o PMC é muito necessário, sendo capaz de minimizar a ocorrência de agravos de saúde e evitar transferências dos idosos para hospitais e Instituições de Longa Permanência para Idosos (Ilpi). As comorbidades crônicas aumentam as demandas de cuidado em saúde e geram situações que podem ser manejadas pelo cuidador do PMC. O envelhecimento populacional requer o planejamento de estratégias e políticas públicas voltadas para o provimento de cuidados contínuos para idosos, incluindo aqueles que vivem em comunidades. O PMC surge como alternativa intersetorial para auxiliar nessa questão. CONCLUSÕES: O PMC pode ser considerado um modelo de boa prática a ser expandido para outras localidades, entretanto existem lacunas que necessitam ser rediscutidas para que seus processos sejam aprimorados e seus resultados potencializados.
Assistência odontológica à pessoa com deficiência: discricionariedade na linha de frente
Authors: Carneiro Joana Danielle Brandão , Pereira Ana Paula Chancharulo de Moraes , Bousquat Aylene , Frazão Paulo
Published: December 2023

OBJETIVO: Descrever a influência da discricionariedade dos profissionais e organizações da linha de frente na implementação de diferentes formas de acesso à assistência odontológica especializada na Rede de Cuidados à Pessoa com Deficiência. MÉTODOS: Estudo de caso em duas regiões de saúde brasileiras cujo acesso à assistência odontológica especializada era distinto, com análise documental e entrevista com atores-chave, entre julho e dezembro de 2019. RESULTADOS: Na região com acesso referenciado, observou-se que a atenção primária à saúde (APS) tinha centralidade no cuidado e o planejamento/avaliação faziam parte da rotina institucional dos serviços. Na região onde o agendamento era possível por demanda espontânea, notou-se trocas episódicas de informação entre as unidades de APS e as especializadas; o papel de coordenação do cuidado não era um atributo das equipes de APS e as atividades de planejamento/avaliação não estavam incorporadas à rotina das organizações. CONCLUSÕES: A implementação da política de assistência odontológica especializada à pessoa com deficiência se mostrou dependente da coordenação da APS e da condução de atividades de planejamento/avaliação voltadas à construção de uma rede de cuidados integrada e sujeita ao poder discricionário dos profissionais e das organizações da linha de frente, sugerindo que o ambiente relacional e institucional possui um papel importante no processo de implementação de políticas públicas em um sistema descentralizado e regionalizado de saúde.
Prevalence and predictors of breastfeeding in the MINA-Brazil cohort
Authors: Mosquera Paola S. , Lourenço Bárbara H. , Matijasevich Alicia , Castro Marcia C. , Cardoso Marly A.
Published: December 2023

OBJECTIVE: To describe the prevalence and factors associated with exclusive (EBF) and continued breastfeeding (BF) practices among Amazonian children. METHODS: Data from 1,143 mother-child pairs recorded on the Maternal and Child Health and Nutrition in Acre (MINA-Brazil) birth cohort were used. Information on EBF and BF was collected after childbirth (July 2015–June 2016) and during the follow-up visits at 1 and 6 months postpartum, 1, 2, and 5 years of age. For longitudinal analysis, the outcomes were EBF and BF duration. Probability of breastfeeding practices were estimated by Kaplan-Meier survival analysis. Associations between baseline predictors variables and outcomes among children born at term were assessed by extended Cox regression models. RESULTS: EBF frequencies (95% confidence interval [95%CI]) at 3 and 6 months of age were 33% (95%CI: 30.2–36.0) and 10.8% (95%CI: 8.9–12.9), respectively. Adjusted hazard ratio for predictors of early EBF cessation were: being a first-time mother = 1.47 (95%CI: 1.19–1.80), feeding newborns with prelacteals = 1.70 (95%CI: 1.23–2.36), pacifier use in the first week of life = 1.79 (95%CI: 1.44–2.23) or diarrhea in the first two weeks of life = 1.70 (95%CI: 1.15–2.52). Continued BF frequency was 67.9% (95%CI: 64.9–70.8), 29.3% (95%CI: 26.4–32.4), and 1.7% (95%CI: 0.9–2.8) at 1, 2 and 5 years of age, respectively. Adjusted hazard ratio for predictors of early BF cessation were: male sex = 1.23 (95%CI: 1.01–1.49), pacifier use in the first week of life = 4.66 (95%CI: 2.99–7.26), and EBF less than 3 months = 2.76 (95%CI: 1.64–4.66). CONCLUSIONS: EBF and continued BF duration among Amazonian children is considerably shorter than recommendations from the World Health Organization. Significant predictors of breastfeeding practices should be considered for evaluating local strategies to achieve optimal breastfeeding practices.
Gassendi and the Low Countries: Introduction
Authors: Bellis Delphine
Published: December 2023

This introduction summarises the nature of the strong intellectual links existing between the French philosopher Pierre Gassendi (1592–1655) and the Low Countries. It retraces the main steps of his trip to the Spanish Low Countries and the Dutch Republic in 1629, and the importance of this trip for the development of his philosophy, as well as the epistolary network with his correspondents from that area, especially in the field of astronomy. Scholars in the Low Countries were receptive to atomistic theories, empiricism, and anti-dogmatism, all of which are central to Gassendi’s philosophy. Gassendi’s philosophy also provided arguments against Descartes’s metaphysics, and helped disseminate Galileo’s mechanics in the Low Countries. Gassendi’s influence in the Low Countries lasted beyond his death, as can be seen in the philosophy of Spinoza and Bayle.
Atomism and Cartesianism: Gassendi and Gorlaeus (and More) in Utrecht Disputations in the 1650s
Authors: Bos Erik-Jan
Published: December 2023

In the 1650s, two professors of philosophy at the University of Utrecht defended atomism. Interestingly, one of them, Johannes de Bruyn, is considered to be a staunch Cartesian, while the other, Daniel Voet, was a neo-Aristotelian and strongly opposed to Descartes’s philosophy. This article examines this curious situation and analyses the theories of both professors. While converging with Gassendi on several crucial points, their theories relied mainly on other sources. Since De Bruyn’s atomistic view has never been studied before, the main part of the article is devoted to him and his sources. Surprisingly, it turns out that David Gorlaeus was a source of inspiration for De Bruyn’s development of a new type of Cartesianism.
Perseverare in (suo) Esse: Gassendi and Spinoza against Descartes
Authors: Le Gendre Samuel
Published: December 2023

This contribution focuses on the issue of creatures’ conservation in being. The aim is as follows: to demonstrate that the Cartesian position is significantly different from the positions adopted by Gassendi and then by Spinoza. Indeed, both, in contrast to Descartes, adopt a principle of metaphysical inertia, which parallels their principle of physical inertia. If Gassendi can conceive of this principle of metaphysical inertia, it is because he really distinguishes between creation and conservation. If Spinoza, who owes it to his reading of the 5th Objections and Replies, can conceive of his principle, it is because he distinguishes between ideal essence and actual essence.
AICAR Induces AMPK-Independent Cell Death in Adult T-Cell Leukemia/Lymphoma and Has Anti-Tumor Activity
Authors: Kozako Tomohiro , Aikawa Akiyoshi , Ohsugi Takeo , Honda Shin-Ichiro
Published: December 2023

Introduction: Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell leukemia/lymphoma caused by human T-cell lymphotropic virus type I (HTLV-1) and has a poor outcome. Recently, we reported that AMPKα, the catalytic unit of AMP-activated protein kinase (AMPK), is highly expressed in cells from patients with ATL and that an AMPK inhibitor had anti-tumor activity in ATL mice 1. On the other hand, acadesine or 5-aminoimidazole-4-carboxamide riboside (AICAR) is anAMPK activator, and was recently shown to have tumor suppressive effects on B cell chronic lymphocytic leukemia via the activation of AMPK. However, the effect of AICAR on the death of ATL-related cell lines is unknown. This study evaluated the effects of AICAR on death in ATL-related cell lines and its anti-tumor activity.

Results: We demonstrated that AICAR inhibited the proliferation of ATL-related cell lines (S1T, MT-1 and MT-2) but not non-HTLV-1-infected Jurkat cells and peripheral blood mononuclear cells from healthy individuals. However, AICAR did not increase the phosphorylation levels of AMPKα. We found that AICAR increased annexin V-positive cell numbers in the sub-G0/G1 phase, and decreased the mitochondrial membrane potential and caspase-3/8/9 activation, which are hallmarks of apoptosis. However, AICAR did not increase the phosphorylation levels of AMPKα. On the other hand, HTLV-1 Tax, an HTLV-1-encoded oncogenic factor, expression did not affect AICAR-induced cell death. Moreover, AICAR induced the expression of death receptors (DR) DR4 and DR5 in vitro. Furthermore, AICAR inhibited the growth and infiltration of S1T cells transplanted subcutaneously in NOD/SCID/gamma mice.

Conclusion: This is the first evidence to demonstrate the AMPK-independent effects of AICAR on death in ATL-related cell lines and its anti-tumor activity. Thus, AICAR might be a candidate for the treatment of ATL.

Disclosures : No relevant conflicts of interest to declare.

1. Aikawa A, Kozako T, Uchida Y, et al. Cell death induced by dorsomorphin in adult T-cell leukemia/lymphoma is AMPK-independent. Febs j. 2020;287(18):4005-4015.
Single-Cell Genomics Details the Maturation Block in BCP-ALL and Identifies Therapeutic Vulnerabilities in DUX4-Rearranged Cases
Authors: Thorsson Hanna , Henningsson Rasmus , Puente-Moncada Noelia , Sjöström Ludvig , Ågerstam Helena , Peña-Martínez Pablo Enrique , Sandén Carl , Rissler Marianne , Castor Anders , Marquart Hanne Vibeke , Modvig Signe , Paulsson Kajsa , Pronk Cornelis , Schmiegelow Kjeld , Hyrenius Wittsten Axel , Orsmark-Pietras Christina , Lilljebjörn Henrik PhD , Fioretos Thoas
Published: December 2023

B cell progenitor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood malignancy. It is initiated by multiple genetic alterations, causing a maturation arrest and accumulation of abnormal progenitor B cells. Current treatment protocols with chemotherapy have led to favorable outcomes, but are associated with significant toxicity and risk of side effects, highlighting the necessity for highly effective, less toxic, targeted drugs that also show efficacy in children experiencing relapse.

We have used multimodal single-cell sequencing to delineate the transcriptional, epigenetic, and immunophenotypic characteristics of 23 childhood BCP-ALLs, including the BCR::ABL1-positive, ETV6::RUNX1-positive, high hyperdiploid, and recently discovered DUX4-rearranged subtypes. In total, 188,546 single cells derived from 23 BCP-ALLs and 9 normal bone marrow samples were profiled using the 10X Genomics platform. Cellranger multi and atac count (10X Genomics) were used to generate read count matrices. Further analysis was performed using Seurat and Signac. The in-house developed program SingleCellProjections was used to create a normal bone marrow reference graph onto which the BCP-ALL data was projected.

Projection of the ALL cells along the normal B cell differentiation axis, revealed a diversity in the maturation block between the different BCP-ALL subtypes. Whereas the BCR::ABL1-, ETV6::RUNX1-positive and high hyperdiploidy cells mainly showed similarities to normal pro-B cells, the DUX4-rearranged ALL cells also displayed a transcriptional signature resembling mature B cells. In addition, the blast population in DUX4-rearranged ALLs showed multilineage priming toward non-hematopoietic cells, myeloid and T cell lineages, but also an activation of PI3K/AKT signaling that sensitized the cells to PI3K inhibition. Finally, we show that chimeric antigen receptor T cell therapy targeting the upregulated myeloid receptor CD371 (CLL-1), effectively eliminates DUX4-rearranged ALL cells. Our results provide a detailed characterization of BCP-ALL at the single-cell level and reveal therapeutic vulnerabilities in the DUX4-rearranged subtype with important implications for the understanding of ALL biology and new therapeutic strategies.
GI Amyloid: More Than a Heavy Heart
Authors: Forbes Shari De Anna , Agudelo Miguel , Gutierrez Leandro , Ogunnaya Frances Ugonne
Published: December 2023

Amyloid transthyretin (ATTR) amyloidosis is caused by the accumulation of insoluble transthyretin (TTR) amyloid fibrils. These proteins can build up in various organ systems such as the musculoskeletal, gastrointestinal, and ocular system. However, there is usually a predilection for the heart and nervous system [1]. ATTR comprises approximately 16% of GI amyloid cases, with the small bowel being the most common area of involvement [2]. Symptoms typically include abdominal pain, nausea and vomiting, unintentional weight loss, diarrhea, and constipation. Given the rarity of the disease, we present a case of biopsy proven ATTR GI amyloidosis to raise awareness and, consequently, aid in early recognition. Our patient is a 48-year-old female with a medical history of substance use disorder who had multiple evaluations for complaints of chest discomfort and gastrointestinal symptoms including nausea, vomiting and diarrhea. Initial evaluation included an echocardiography which found severe left ventricular hypertrophy. Given her significant family history of myocardial infarction, a left cardiac catheterization was completed, however, this revealed normal coronary vasculature. Subsequently, the patient started medical therapy for heart failure with preserved ventricular function pending further testing. Despite medical management, the patient developed worsening symptoms of heart failure warranting repeat echocardiography which showed a significant reduction in ejection fraction. In addition to the patient's worsening cardiac symptoms, she continued to have refractory gastrointestinal symptoms and developed new epigastric pain. Therefore, the patient underwent upper endoscopy with discovery of abnormal peristalsis. After which, a gastric emptying study was done, resulting in a diagnosis of gastroparesis. With the constellation of findings i.e., the pattern of ventricular hypertrophy, lack of hypertensive and coronary artery disease, as well as gastroparesis without a known etiology, there was suspicion for systemic infiltrative disease, which led to further investigation. Gastric, small, and large bowel biopsies confirmed amyloid deposits. The patient also underwent a Tc99m-PYP scan which revealed evidence of cardiac amyloidosis; monoclonal protein analysis test was negative, and a cardiac biopsy showed a profile consistent with amyloid transthyretin type. The patient remained on pharmacologic therapy for gastroparesis and has been referred to cardiac transplantation services for further management.Our case highlights that amyloidosis, including GI amyloidosis, has the potential to go unrecognized due to non-specific signs and symptoms. Clinicians should therefore always have a high index of suspicion as GI involvement in systemic amyloidosis, regardless of protein subtype, is common. This high index of suspicion will allow for the appropriate pathologic examination to be pursued, and ultimately the appropriate management.
Autoimmune Neutropenia of Infancy Is Almost Exclusively Caused By IgG Antibodies
Authors: Sachs Ulrich J. , Braun Matthias , Bein Gregor , Bayat Behnaz
Published: December 2023

Background

The relevance of IgM antibodies in autoimmune mediated hemocytopenias remains a matter of debate. For autoimmune neutropenia, conflicting results were published. This study was performed as part of the Giessen Neutropenia Registry, which prospectively included children with suspected autoimmune neutropenia.

Methods

Children with suspected autoimmune neutropenia were prospectively enrolled and data central to their suspected diagnosis were collected over 3 years. Sera were tested for the presence of autoantibodies against neutrophils by granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT). The presence of IgG and IgM antibodies was assessed in a subgroup of patients with positive initial GIFT in whom spontaneous remission of their neutropenia was documented.

Results

A total of 406 children were included in the study. A remission was reported for 114 patients during the study period. Of those, 96 children (84%) had an initial positive GIFT. Their median age at diagnosis was 11 months (7-17.5), and their mean neutrophil count was 293 (±267)/µL, ranging from 0 to 975. In total 75/96 (78%) of children had at least one documented infection at diagnosis. In 29/96 (30%), a bone marrow aspirate was available. At the documented time point of remission, children were 27 months (18-41) old. In the initial sample send for diagnosis, IgG antibodies against neutrophils were detected in 94/96 children (98%), and IgM antibodies were detected in 2/96 (2%). We did not observe children with autoantibodies of both Ig classes.

Conclusion

To our knowledge, this is the first study to demonstrate the contribution of IgG or IgM antibodies in a well-defined clinical cohort with a typical course including, spontaneous disease remission. IgG antibodies were present in 98%. Only very rarely, IgM antibodies can be detected. We conclude that in general, screening for IgG autoantibodies is appropriate as a first diagnostic step. In cases with strong clinical suspicion but negative GIFT with anti-IgG, anti-IgM testing may be considered.
Early M-Protein Immune Reconstitution after Autologous Hematopoietic Stem Cell Transplantation Is a Good Prognostic Marker for Patients with High-Risk Cytogenetic Multiple Myeloma
Authors: Zhu Huihui , Li Juan
Published: December 2023

OBJECTIVE: The presence of transient abnormal protein banding (i.e. M-protein immune reconstitution) in serum immunofixation electrophoresis after autologous hematopoietic stem cell transplantation in patients with multiple myeloma has been reported, and patients with high-risk cytogenetics tend to have poor prognosis; the purpose of this paper is to investigate the impact of post-transplant M-protein immune reconstitution on the prognosis of patients with high-risk cytogenetic multiple myeloma;

METHODS: To retrospectively analyze the clinical data of 290 newly diagnosed multiple myeloma patients from August 1, 2008 to July 31, 2021 at the First Affiliated Hospital of Sun Yat-sen University, all of whom underwent sequential autologous hematopoietic stem cell transplantation after induction therapy, and to analyze and compare the clinical characteristics and prognostic survival of patients with and without M-protein immune reconstitution;

RESULTS: M-protein immune reconstitution was observed in 25.9% (75/290 patients), the most common type of immunoglobulin was IgG-λ. The median time to obtain M-protein immune reconstitution was 3 months (1-38 months) and the median duration was 4 months (1-39 months) after transplantation, and there were no statistical differences in disease stage, tumor load and cytogenetics between the M-protein immune reconstituted and non-M-protein immune reconstituted groups. The CR rate and MRD negativity were higher in the M-protein immune reconstitution group (85.3% vs 69.3%, p=0.013, 81.9% vs 66.5%, p=0.014), and although there were no statistical differences in PFS and OS between the M-protein immune reconstitution group and the group without M protein immune reconstruction, the overall median survival time was longer in the M protein immune reconstruction group (80 vs 72m, p=0.096. not reached vs 105m, p=0.344). Among patients in the cytogenetic high-risk group, access to M-protein immune reconstitution predicted better PFS and OS (80 vs 31m, p=0.010. not reached vs 79m, p=0.026). Also in R-ISS stage III patients, PFS and OS were better in patients who obtained M-protein immune reconstitution (80 vs 20m, p=0.034. 57 vs 32m, p=0.137).

CONCLUSION: Better prognosis in M-protein immune reconstitution patients may be associated with the acquisition of a deeper response, but in high-risk patients, early acquisition of M-protein immune reconstitution may suggest a better prognosis.
TBI/Ratg-Based Conditioning for Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in 11 Cases of Chemotherapy-Resistant Advanced-Stage Peripheral T-Cell Lymphoma
Authors: Zhu JUN , Xu Rong , Wang Chun , Zhao Chuxian , Jiang Ying , Wei Daolin , Shao Shan , Liu Huixia , Li Su
Published: December 2023

Objectives: To evaluate the clinical outcomes and safety of haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT)with total body irradiation (TBI)/rabbit Anti-thymocyte globulin (rATG) based conditioning regimen in chemotherapy-resistant advanced-stage peripheral T-cell lymphoma (PTCL).

Methods: From September 2019 to December 2022, eleven chemotherapy-resistant advanced-stage PTCL patients who underwent haplo-HSCT were enrolled in our study. All of them received TBI/rATG-based conditioning regimen in our centers.

Results: ①Among 11 patients, there were 6 males and 5 females with a median age of 40(range：22~58) years old. Six cases of them are peripheral T-cell lymphoma not otherwise specified (PTCL NOS), 3 cases are angioimmunoblastic T-cell lymphoma (AITL), 1 case is large-cell transformation of mycosis fungoides (MF-LCT), and 1 case is T-cell large granular lymphocytic leukemia(T-LGLL). The Lugano stage was III or IV in all cases, and 8 patients had B symptoms. The median number of previous chemotherapy exposure before transplantation was 4 (range: 2~10) lines and the disease status before transplantation was progressive diseases (PD) in all cases. The median time from diagnosis to transplantation was 17(range：6~36) months.②The conditioning regimen consisted of TBI 2Gy d-8, 4Gy from day-7 to -6, rATG 2.5 mg/kg/d day-5 to -2, etoposide 15mg/kg/d day-5 to -4, cyclophosphamide (CTX) 50mg/kg/d, day-3 to -2. The patients with central nervous system involvement received a regimen of thiotepa 5 mg/kg/d， from day -5 to -4 instead of CTX and etoposide, and add 2.0 g/m2 of cytarabine twice a day, from day -3 to day -2 into the conditioning.③All patients were successfully engrafted. Only one patient developed Grade III-IV acute graft-vs-host disease (aGvHD). Among the 8 survivors, 4 cases developed chronic graft-vs-host disease (cGvHD).④After transplantation, CR was obtained in 9 patients. ⑤Regimen related toxicities: all were non-fatal. Hematopoietic suppression occurred in all patients after conditioning. Three patients had diarrhea and four had mucositis and three had elevated transaminase/bilirubin levels. Seven patients had infections.⑥The 1-year cumulative non-relapse mortality (NRM) and 1-year cumulative incidence of relapse (CIR) was 22.5±14.0% and 20.2±12.7%, respectively. The 1-year overall survival (OS) and 1-year disease-free survival (DFS) was 72.7±13.4% and 63.6±14.5%, respectively

Conclusions: TBIand rATG based conditioning regimen is effective and safe for haplo-HSCT in chemotherapy-resistant advanced-stage PTCL.
Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant Cyclophosphamide in the Chilean National Health System. a Single Center Study
Authors: Puga Bárbara , Benavente Rafael , Bass Francisca , Molina M. Javiera , Andrade Alejandro , Majlis Alejandro , Cabrera Maria Elena , Undurraga Soledad
Published: December 2023

Haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide (Haplo-PTCy) is the most common transplantation modality in low-and-middle-income countries (LMIC). Registry data has shown comparable outcomes when using haploidentical donors versus Matched Unrelated Donors (MUD) in patients with acute leukemias. In the Chilean Public Health System Haplo-PTCy was incorporated in 2016 for adults up to 60 years old.

We analyzed all adult patients who received an Haplo-PTCy at Hospital del Salvador, in a prospective registry study between 2016 and 2021. The primary outcome was overall survival (OS). Secondary outcomes were event-free survival (EFS), cumulative incidence of relapse, and incidence of grade II-IV acute graft-versus-host disease (aGVHD) at day +100. Overall survival and EFS were estimated using the Kaplan-Meier method. The cumulative incidence of relapse was calculated using relapse as the primary event and death without relapse as a competing event. Acute GVHD is shown as absolute incidence at day +100. All statistical analyses were performed with R. This study was done in compliance with the Helsinki Declaration and was approved by the Institutional Review Board.

Eighty-five Haplo-PTCy were performed in 82 patients (Table 1). Three-second Haplo-PTCy were excluded from this analysis. The median age was 25 years (range, 15-51), and 65% were male. Ninety-four percent of patients had a neoplastic disease (77/82), and the most common diagnosis was acute lymphoblastic leukemia (57%). Forty-seven percent proceeded to transplant in the first complete response. Most of the patients (76%) presented a low hematopoietic cell transplantation (HCT)-specific comorbidity index. Conditioning was mostly myeloablative (96%). The median dose of CD34+ cells infused was 8.1 x 106/kg (range, 2.4-10.0). No patient needed a desensitization regimen. Cytokine release syndrome (CRS) was common (86%) but no grade 3 CRS was observed. Primary graft failure was observed in one patient (1.2%). Poor graft function was observed in 11 patients (13%). Five patients (6.1%) died before engraftment. The incidence of grade II-IV aGVHD at day +100 was 29% (grade IV was not observed). With a median follow-up of 33 months (range 0-84), the estimated 3-year OS and EFS were 68.3% (95% CI 59-79%) and 64.6% (95% CI 55-76%), respectively (Figure 1). In patients with neoplastic disease (n=77), the 3-year cumulative incidence of relapse was 23% (95% CI 15-33%).

Haplo-PTCy is feasible in LMIC. This cohort of cases, mostly young patients with neoplastic disease, shows encouraging survival with an acceptable aGVHD and relapse incidence.
Identifying and Addressing Knowledge and Confidence Gaps Regarding the Management of Patients with Sickle Cell Disease Via Engaging Continuing Medical Education
Authors: Robinson Katie , Esgro Robert A. , Cooper Simon , LoPresti Michael , Carson Benjamin
Published: December 2023

Introduction: While there have been recent advances in therapeutic options for the management of patients with sickle cells disease (SCD), hematology providers remain challenged by how to deliver an individualized approach to care, negatively impacting patient outcomes. To address this practice gap and identify drivers that underlie persisting challenges, an interactive continuing medical education (CME) activity was developed and implemented.

Methods: Vindico Medical Education provided an interactive web-based CME activity on CME.Healio.com that was available for credit for one year starting August 31, 2022. The activity included opportunities for interaction with the content to encourage engagement, transfer knowledge, improve confidence, and encourage appropriate practice patterns. Impact of education was measured by comparing paired pre- and post-test responses.

Results: As of July 2023, 221 hematology/oncology providers, including 116 MDs and advanced practice providers (APPs) and 105 nurses, who each see an average of 4 patients with SCD per month participated in the education. At baseline, scores on questions related to the latest evidence regarding new SCD therapies were low in both professional cohorts - an average 30% for MD/APPs and 16% for nurses. Moreover, 95% of HCPs in both cohorts lacked confidence in their knowledge of these agents and their appropriate use. This lack of knowledge and confidence translated into practice gaps. Specifically, 48% of those involved in treatment decisions indicated in the pre-test that they had never used a newer option for SCD management, and only 17% reported that they always consider the latest evidence when individualizing treatment for patients. On a post-test, however, the MD/APP and nurse cohorts scored an average of 81% and 84%, respectively, indicative of a robust impact of the education on clinician knowledge. Similarly, there was a 41% absolute increase in clinician confidence in understanding the latest evidence. These gains in knowledge and confidence translated into post-education planned practice improvements, with completers 22% more likely to apply this knowledge to clinical decision-making.

Conclusion: Hematology/oncology providers lack knowledge and confidence regarding the latest evidence in SCD treatment. While the use of interactive CME led to robust gains in knowledge and confidence, follow-up case-based education is needed to facilitate the application of knowledge to practice while continuing to improve clinician confidence.
Notch1 Regulates Hepatic Thrombopoietin Production
Authors: Sun Yueyue , Tong Huan , Zeng Lingyu , Xu Kailin , Qiao Jianlin
Published: December 2023

Notch signaling is highly conserved and regulates cell-fate decisions in several developmental processes and cell functions. However, a role for Notch in hepatic thrombopoietin (TPO) production has not been described. We noted that mice with a deficiency in hepatic Notch1 had thrombocytopenia, and so investigated TPO production and other features of platelets in these mice. We found that the liver ultrastructure and hepatocyte function were comparable between control mice and Notch1-deficient mice. However, the Notch1-deficient mice had significantly lower plasma TPO and hepatic TPO mRNA levels, concomitant with lower numbers of circulating platelets and impaired megakaryocyte differentiation and maturation. Addition of exogenous TPO rescued megakaryocyte maturation and circulating platelet numbers. Additionally, JAK2/STAT3 phosphorylation was significantly inhibited in Notch1-deficient hepatocytes. RNA-seq analysis showed significantly reduced JAK-STAT signaling. JAK2/STAT3 phosphorylation and TPO production was also impaired in purified cultured Notch1-deficient hepatocytes after treatment with desialylated platelets. Interestingly, Notch1 deficiency downregulated the expression of HES5 but not HES1. Moreover, desialylated platelets promoted the binding of HES5 to JAK2/STAT3, leading to JAK2/STAT3 phosphorylation and pathway activation. Furthermore, blockage of Dll4 on desialylated platelets inhibited hepatocyte Notch1 activation and HES5 expression, JAK2/STAT3 phosphorylation and subsequent TPO production. In conclusion, our study identifies a novel regulatory role of Notch1 in hepatic TPO production, indicating that it might be a target for modulating TPO level.
Clinical Characteristics and Prognosis of Primary Plasma Cell Leukemia and Newly Diagnosed Multiple Myeloma Under the New IMWG Definition Criteria
Authors: Guan Jiaheng , Chen Bao-An
Published: December 2023

Background: Recently, the International Myeloma Working Group (IMWG) has recommended new primary plasma cell leukemia (pPCL) definition criteria, which require the presence of ≥ 5% circulating plasma cells in peripheral blood smears. The objective of this study was to investigate the clinical characteristics and prognosis of new-defined pPCL and newly diagnosed multiple myeloma (NDMM).

Methods: This was a single-center, retrospective study including patients diagnosed with new-defined pPCL or NDMM at Zhongda Hospital, China, between January 2010 and December 2022.

Results: There were 23 pPCL patients and 264 NDMM patients in our cohort. Generally, pPCL patients were younger than NDMM patients (median diagnostic age: 63 vs. 67 years old, p=0.018). The 1q21+ aberration was predominantly found in NDMM (p= 0.038) whereas t(11;14) dominated in pPCL (p= 0.017). Notably, pPCL exhibited a lower platelet level (p< 0.001) and a higher frequency of non-hyperdiploid karyotypes (p= 0.03) in contrast to NDMM. The median overall survival (OS) and progression-free survival (PFS) in NDMM were notably superior to those observed in pPCL (HR: 0.41, p= 0.001, HR: 0.38, p< 0.001, respectively). Interestingly, the OS in NDMM was 3 times longer than that in pPCL in females (p< 0.01) while no difference was found between NDMM and pPCL in males (p= 0.078). Moreover, NDMM patients treated with proteasome inhibitor (PI)-based treatment showed a significantly better prognosis than pPCL patients receiving the same treatment (OS: p< 0.01, PFS: p< 0.01, respectively). Similar findings were observed for patients undergoing either autologous stem cell transplantation (ASCT) or CD38 antibody treatment, both presenting a favorable prognosis in NDMM. However, no significant difference emerged between the two groups in terms of immunomodulatory drugs (IMiDs)-based or PI+IMiDs-based regimens. Multivariate analysis indicated elevated lactate dehydrogenase (LDH) was an independent predictor of adverse prognosis in NDMM (HR: 3.12, p<0.01).

Conclusion: Our study revealed the clinical features and prognosis of pPCL and NDMM patients according to the new diagnostic criteria. The findings highlighted a generally improved prognosis in NDMM compared to pPCL, especially among female patients or those treated with PI-based regimens. It is important to note that our study had a limited sample size, potentially introducing some bias. We hope well-designed and long-term follow-up studies can be conducted to provide more reliable results.