bluuebunny/crossref_metadata_2025 huggingface dataset:
Upgrading the fiscal rules system in the European Union and prospects for their reforms in Ukraine
Authors:   NGO “Growford Institute”, BOHDAN Tetiana
Published: May 2023

Introduction. In 2022 and 2023 fiscal rules in Ukraine were suspended by amendments to the Budget Code, although after the end of war the negotiation process with the EU on its enlargement will put the issue of resumption of the fiscal rules in Ukraine and their alignment with the EU norms on the economic reforms’ agenda in Ukraine. Problem Statement. Restoration of the system of fiscal rules in Ukraine and its new substantive filling on the way of Ukraine’s preparation for the EU accession taking into account the experience of implementation of the supra-national fiscal rules in the EU and challenges for the reforms of the budgetary framework in the EU member states. Purpose – drawing lessons of functioning of the numerical fiscal rules in the EU, reviewing the components of transformation of the budgetary framework and mechanisms of the fiscal policy surveillance from the side of the EU supra-national bodies and eventually, on their basis, specifying the core directions of reforming fiscal rules in Ukraine for their approximation to the EU standards. Methods. General scientific and special methods are applied: analysis and synthesis, description and comparison, historical method, method of theoretical generalization and abstract-logical method. Results. The article highlights the essence of fiscal rules as important constituents of modern fiscal institutions, shows the quantitative indicators of extension of the fiscal rules across the world and their common combinations. It reveals the main trends in modification of the fiscal rules and validation of the escape clauses in the course of corona-crisis. The author summarizes the mechanisms of budget deficit regulation, containment of public expenditure growth and limiting public debt level in the EU member states with a focus on the provisions of the Stability and Growth Pact and of the EU Regulations, which specify the tools of application of the Pact and Treaty on the Functioning of the European Union. The author synthetizes the key dimensions of current transformation of the EU fiscal rules with an emphasize on the instruments of fiscal policy surveillance in the EU member states and targeting fiscal policy at achieving green and digital transition by their economies with simultaneous debt sustainability goal. Policy proposals are devised for upgrading the system of fiscal rules in Ukraine and their validation after finishing the war. Conclusions. Incorporation of debt limit and budget balance ceiling across the sector of general government into the budgetary legislation of Ukraine, as well as of net primary expenditure rule aimed at restoration of the debt sustainability, as well as mechanisms of implementation of the fiscal rules and independent monitoring of the fiscal rules observance in line with the EU standards (over the medium run) would contribute to securing macro-financial stability in Ukraine and accelerate the economic and political integration of Ukraine with the EU.
ANÁLISE DE ERROS EM RESOLUÇÃO DE PROBLEMAS ENVOLVENDO SÓLIDOS GEOMÉTRICOS NUMA TURMA DE SEGUNDO ANO DO ENSINO MÉDIO DA REDE PÚBLICA
Authors: Barbosa Aline Mauricio , Silva da Costa Marcos Vinícius
Published: May 2023

O objetivo deste trabalho foi analisar os principais tipos de erros, cometidos por estudantes de uma turma do segundo ano do Ensino Médio da rede pública, na resolução de problemas envolvendo áreas de superfícies e volumes de sólidos geométricos. Esses alunos responderam a um questionário diagnóstico, contendo problemas sobre essa temática. Depois eles participaram de atividades com materiais manipuláveis, realizando planificações, montagem de sólidos geométricos e estudando aspectos conceituais. Após isso, eles resolveram novos problemas sobre os conteúdos mencionados e escreveram comentários sobre as atividades realizadas. Para avaliar as respostas desses alunos, usou-se a metodologia de análise de erros segundo Cury (2019). Houve vários equívocos na interpretação de enunciados, confusões conceituais, erros aritméticos, além de várias respostas em branco ou sem fundamento. A análise de erros cometidos pelos alunos se constitui numa importante aliada para o docente repensar a sua prática e para gerar novas oportunidades de ensino-aprendizagem.
RESOLUÇÃO DE PROBLEMAS NAS TESSITURAS DAS EXPERIÊNCIAS MATEMÁTICAS NO 5.° ANO DO ENSINO FUNDAMENTAL
Authors: Ferreira Michelle Gonçalves , Alves de Oliveira Sandra
Published: May 2023

Este artigo tem como objetivo compreender os pressupostos teórico-metodológicos da resolução de problemas nas tessituras das experiências matemáticas narradas por estudantes do 5.º ano, nos processos de ensino-aprendizagem de conteúdos matemáticos. Nesta pesquisa de abordagem qualitativa, as experiências desses estudantes com práticas de resolução de problemas em aulas de matemática são expressas por meio de narrativas orais e escritas, produzidas em contextos online, via aplicativo WhatsApp, no segundo semestre de 2020, devido à pandemia da Covid-19 que inviabilizou a vivência de atividades presenciais na escola. A produção de dados foi realizada em seis encontros investigativos no âmbito da pesquisa desenvolvida no curso de Especialização em Ensino de Ciências e Matemática nos Anos Iniciais da Faculdade de Educação da Universidade Federal de Juiz de Fora. As narrativas dos sete estudantes participantes revelam a importância de problematizar a práxis, visto que as operações de adição, subtração, multiplicação e divisão estudadas e compartilhadas, na maioria das histórias de experiências com a resolução de problemas, precisam ser matematizadas nas perguntas, na solução e na criação de problemas, para que os estudantes dialoguem com os resultados encontrados e com as diferentes estratégias desenvolvidas no processo da resolução dos problemas matemáticos. O estudo revelou que os processos de ensino-aprendizagem da matemática precisam ser repensados constantemente, para propiciar aos estudantes práticas matematizadas, numa interação dialógica e problematizadora.
ENSINO DA GRANDEZA VOLUME POR MEIO DA RESOLUÇÃO DE PROBLEMAS
Authors: Jucá Rosineide de Sousa , Costa Ninarosa Tavares da , Ramos Kymberli Luana Santos
Published: May 2023

O objetivo desse trabalho é relatar uma experiência desenvolvida por meio da exploração e resolução de problemas para a construção do conceito de volume com alunos do 6º e 7º do ensino fundamental. O caminho metodológico desse trabalho seguiu as orientações do design research, um tipo de metodologia qualitativa, que inclui três fases de uma investigação na modalidade de experiência de ensino: a preparação da experiência, a experimentação em sala de aula e a análise retrospectiva. Para isso, elaboramos uma proposta de ensino por meio da exploração e resolução de problemas sobre conteúdo de volume do prisma e do cilindro. O referencial teórico adotado traz discussões sobre   resolução de problemas e sua importância no ensino de matemática, como também sobre construção de conceitos. Os resultados apontaram que os alunos que participaram do experimento de ensino apresentaram compreensão do conceito de volume, e se mostraram motivados ao participar das atividades.
O PRINCÍPIO DE CAVALIERI POR MEIO DA RESOLUÇÃO DE PROBLEMAS: UMA EXPERIÊNCIA COM FORMAÇÃO DE PROFESSORES
Authors: Zanelato Colaço Amanda , Bar de Figueiredo Elisandra , Bihuna de Azevedo Eliane
Published: May 2023

Neste artigo, apresentamos o relato de experiência de uma sequência de atividades desenvolvida para abordar o Princípio de Cavalieri por meio da metodologia de Ensino-Aprendizagem-Avaliação de Matemática através da Resolução de Problemas. Essa prática propõe o uso de material concreto e aplicativos dinâmicos no GeoGebra 3D e foi aplicada em uma turma de um curso de Licenciatura em Matemática. A pesquisa foi uma investigação qualitativa de natureza exploratória, cuja experimentação possibilitou identificar as potencialidades e as limitações dos objetos de aprendizagem utilizados e suas influências no ensino e aprendizagem de matemática. Com a aplicação, percebemos a importância do material concreto para a visualização e o uso em conjunto com aplicativos dinâmicos que permitiam simular várias situações. Por outro lado, chamou-nos atenção a falta de experiência dos alunos em trabalhar com aproximações de resultados em problemas experimentais, evidenciando a necessidade de mais práticas com situações semelhantes. Além disso, podemos constatar que os alunos não tinham familiaridade com o Princípio de Cavalieri, usando as fórmulas sem refletir sobre as suas origens. Na formalização, discutimos como esse resultado se aplica no cálculo de volumes de diversos sólidos, ressaltando sua importância na formação de professores e indicando possibilidades de uso também no Ensino Básico.
Global, regional and national burden of endocrine, metabolic, blood and immune disorders 1990-2019: a systematic analysis of the Global Burden of Disease study 2019
Authors: Wu Junyun , Lin Xiling , Huang Xin , Shen Yuyan , Shan Peng-Fei
Published: May 2023

Background

Endocrine, metabolic, blood and immune disorders (EMBID) is a vital public health problem globally, but the study on its burden and global trends was scarce. We aimed to evaluate the global burden of disease and trends in EMBID from 1990 to 2019.

Methods

We extracted the data of EMBID-related on death cases, Age-standardized death rates (ASDRs), disability-adjusted life-years (DALYs), Age-standardized DALY rates, years of life lost (YLLs), Age-standardized YLL rates, years lived with disability (YLDs) and Age-standardized YLD rates between 1990 and 2019 from the Global Burden of Disease 2019, by sex, age, and year at the global and geographical region levels. The Annual rate of change was directly extracted from Global Health Data Exchange (GHDx) and we also calculated the age-related age-standardized rate (ASR) to quantify trends in EMBID-related deaths, DALYs, YLLs and YLDs.

Result

Globally, the EMBID-related ASDRs showed an increasing trend, whereas the DALYs ASR, YLLs ASR and YLDs ASR were decreased between 1990 to 2019. Furthermore, High-income North America and Southern Sub-Saharan Africa had the highest both ASDRs and DALYs ASR, and Southern Sub-Saharan Africa and Caribbean had the highest both YLDs ASR and YLLs ASR in 2019. Males had a higher EMBID-related ASDRs than females, but the DALYs ASR in females were higher than males. The burden of EMBID was higher in older-aged compared to other age groups, especially in developed regions.

Conclusion

Although EMBID-related ASRs for DALYs-, YLLs- and YLDs declined at the global level from 1990 to 2019, but the ASDRs was increasing. This implied high healthcare costs and more burden of ASDRs due to EMBID in the future. Therefore, there was an urgent need to adopt geographic targets, age-specific targets, prevention strategies and treatments for EMBID to reduce negative health outcomes globally.
Decreased bone mass in adolescents with bone fragility fracture but not in young children: a case–control study
Authors: Matkovic Velimir , Goel Prem , Mobley Stacey L. , Badenhop-Stevens Nancy E. , Ha Eun-Jeong , Li Bin , Skugor Mario , Clairmont Albert
Published: May 2023

Background

The incidence of distal forearm fracture due to minimal/moderate trauma shows a bimodal distribution for age at event, with one peak occurring during early adolescence, in both boys and girls and the other one in postmenopausal females. The aim of this study was, therefore, to document whether the relationship between bone mineral density and fracture is different in young children compared with adolescents.

Methods

A matched-pair, case–control study has been conducted to evaluate bone mineral density in 469 young children and 387 adolescents of both sexes, with/without fracture due to minimal/moderate trauma with assurance that the compared groups were equally susceptible to the outcome event. All fractures were radiographically confirmed. The study utilized bone mineral areal density of the total body, spine, hips, and forearm; volumetric bone mineral density of the forearm; and metacarpal radiogrammetry measurements. The study controlled for skeletal development, bone geometry, body composition, hand grip strength, calcium intake, and vitamin D status.

Results

Adolescents with distal forearm fracture have reduced bone mineral density at multiple skeletal regions of interest. This was documented by the bone mineral areal density measurements at multiple skeletal sites (p < 0.001), volumetric bone mineral density measurements of the forearm (p < 0.0001), and metacarpal radiogrammetry (p < 0.001). Adolescent females with fracture had reduced cross-sectional areas of the radius and metacarpals. The bone status of young female and male children with fracture was no different to its controls. Increased body fatness was more prevalent among fracture cases than in controls. Around 72% of young female and male children with fracture had serum 25-hydroxyvitamin D levels below the threshold of 31 ng/ml, compared with only 42% of female controls and to 51% of male controls.

Conclusions

Adolescents with bone fragility fracture had reduced bone mineral density at multiple skeletal regions of interest, whereas this was not the case with younger children. The results of the study may have implications for the prevention of bone fragility in this segment of the pediatric population.
Efficacy and safety of traditional Chinese medicines combined with conventional Western medicines in the treatment of type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials
Authors: Ma Kaile , Zhou Lijuan , Zhang Yanjiao , Zhao Jingyi , Yao Chensi , Tian Chuanxi , Li Min
Published: May 2023

Aims/hypothesis

Through a comprehensive analysis of the clinical randomized controlled trials of traditional Chinese medicine (TCM) combined with conventional western medicine (CWM) in treating type 2 diabetes(T2DM) in the past ten years, the clinical efficacy and safety of different TCMs combined with CWM were explored. This study aimed to provide specific suggestions for clinical guidance on treating T2DM.

Methods

A literature search was conducted in CNKI, WanFang, VIP, CBM, PubMed, Embase, and Web of Science. The search time was limited from 2010 to the present time. The literature type was a controlled clinical trial study of TCM combined with CWM intervention in treating T2DM. The outcome indices of the efficacy evaluation included fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), adverse reactions, and clinical efficacy. Stata 15 and RevMan 5.4 software were used to conduct a network meta-analysis and a traditional meta-analysis.

Results

The results showed that shenqi jiangtang granule combined with sulfonylurea, shenqi jiangtang granules combined with metformin and jinlida granules combined with insulin had significant effects on reductions in FBG, 2hPG and clinical efficacy compared with western medicines alone, which included fasting blood glucose [MD=-2.17, 95%CI=(-2.50, -1.85)], blood sugar at 2 hours after a meal [MD=-1.94, 95%CI=(-2.23, -1.65)], and clinical curative effect [OR= 1.73, 95%CI=(0.59, 2.87)].

Conclusions

TCM combined with CWM has a very significant effect on treating T2DM compared with CWM alone. According to the network meta-analysis, the best intervention measures of different TCMs for different outcome indicators were obtained.

Systematic review registration

identifier 42022350372.
Predictive performance of aldosterone-to-renin ratio in the diagnosis of primary aldosteronism in patients with resistant hypertension
Authors: Bioletto Fabio , Lopez Chiara , Bollati Martina , Arata Stefano , Procopio Matteo , Ponzetto Federico , Beccuti Guglielmo , Mengozzi Giulio , Ghigo Ezio , Maccario Mauro , Parasiliti-Caprino Mirko
Published: May 2023

Background

The systematic use of confirmatory tests in the diagnosis of primary aldosteronism (PA) increases costs, risks and complexity to the diagnostic work-up. In light of this, some authors proposed aldosterone-to-renin (ARR) cut-offs and/or integrated flow-charts to avoid this step. Patients with resistant hypertension (RH), however, are characterized by a dysregulated renin-angiotensin-aldosterone system, even in the absence of PA. Thus, it is unclear whether these strategies might be applied with the same diagnostic reliability in the setting of RH.

Methods

We enrolled 129 consecutive patients diagnosed with RH and no other causes of secondary hypertension. All patients underwent full biochemical assessment for PA, encompassing both basal measurements and a saline infusion test.

Results

34/129 patients (26.4%) were diagnosed with PA. ARR alone provided a moderate-to-high accuracy in predicting the diagnosis of PA (AUC=0.908). Among normokalemic patients, the ARR value that maximized the diagnostic accuracy, as identified by the Youden index, was equal to 41.8 (ng/dL)/(ng/mL/h), and was characterized by a sensitivity and a specificity of 100% and 67%, respectively (AUC=0.882); an ARR > 179.6 (ng/dL)/(ng/mL/h) provided a 100% specificity for the diagnosis of PA, but was associated with a very low sensitivity of 20%. Among hypokalemic patients, the ARR value that maximized the diagnostic accuracy, as identified by the Youden index, was equal to 49.2 (ng/dL)/(ng/mL/h), and was characterized by a sensitivity and a specificity of 100% and 83%, respectively (AUC=0.941); an ARR > 104.0 (ng/dL)/(ng/mL/h) provided a 100% specificity for the diagnosis of PA, with a sensitivity of 64%.

Conclusions

Among normokalemic patients, there was a wide overlap in ARR values between those with PA and those with essential RH; the possibility to skip a confirmatory test should thus be considered with caution in this setting. A better discriminating ability could be seen in the presence of hypokalemia; in this case, ARR alone may be sufficient to skip confirmatory tests in a suitable percentage of patients.
Ketoconazole as second-line treatment for Cushing’s disease after transsphenoidal surgery: systematic review and meta-analysis
Authors: Viecceli Camila , Mattos Ana Carolina Viana , Hirakata Vânia Naomi , Garcia Sheila Piccoli , Rodrigues Ticiana da Costa , Czepielewski Mauro Antônio
Published: May 2023

Introduction

The first-line treatment for Cushing’s disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response.

Methods

We searched for articles that evaluated ketoconazole use in Cushing’s disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels.

Results

After applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism.

Conclusion

Ketoconazole can be considered a safe and efficacious option for Cushing’s disease treatment after pituitary surgery.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).
National oncofertility registries around the globe: a pilot survey
Authors: Ozimek Noelle , Salama Mahmoud , Woodruff Teresa K.
Published: May 2023

Purpose

Oncofertility is an emerging discipline which aims to preserve fertility of young cancer patients. As fertility preservation services have become increasingly available to cancer patients in many countries around the globe, it is crucial to establish a foundation of collaborative reporting to continuously monitor and assess oncofertility practices. This survey study investigates the current global landscape of official national oncofertility registries, a vital tool which allows for surveillance of the field.

Methods

An online pilot survey was conducted to give the opportunity to report official national oncofertility registries available in 2022. Survey questions covered the availability of official national registries for oncofertility as well as the official national registries for cancer and assisted reproductive technologies. Participation in the survey was voluntary, anonymous and for free.

Results

According to our online pilot survey, responses were collected from 20 countries including Argentina, Australia, Brazil, Canada, Chile, China, Egypt, Germany, Greece, India, Japan, Kenya, Philippines, Romania, South Africa, Thailand, Tunisia, UK, USA & Uruguay. Only 3 out of the 20 surveyed countries have well-established official national oncofertility registries; and include Australia, Germany & Japan. The Australian official national oncofertility registry is part of Australasian Oncofertility Registry that also includes New Zealand. The German official national oncofertility registry is part of FertiPROTEKT Network Registry for German speaking countries that also includes Austria & Switzerland. The Japanese official national oncofertility registry includes Japan only and called Japan Oncofertility Registry (JOFR). A supplementary internet search confirmed the aforementioned results. Therefore, the final list of countries around the globe that have official national oncofertility registries includes Australia, Austria, Germany, Japan, New Zealand, and Switzerland. Some other countries such as the USA and Denmark are on their way to establish official national registries for oncofertility care.

Conclusion

Although oncofertility services are expanding globally, very few countries have well-established official national oncofertility registries. By reviewing such a global landscape, we highlight the urgent need for having a well-established official national oncofertility registry in each country to monitor oncofertility services in a way that best serves patients.
Genes in loci genetically associated with polycystic ovary syndrome are dynamically expressed in human fetal gonadal, metabolic and brain tissues
Authors: Azumah Rafiatu , Hummitzsch Katja , Anderson Richard A. , Rodgers Raymond J.
Published: May 2023

Background

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, affecting around 10% of women of reproductive age, with infertility, depression or anxiety, obesity, insulin resistance and type 2 diabetes as risk factors. The cause of PCOS is not known but there is a predisposition to developing PCOS in adult life that arises during fetal or perinatal life. PCOS also has a genetic predisposition and a number of genetic loci associated with PCOS have been identified. These loci contain 25 candidate genes which are currently being studied to define the syndrome. Although the name PCOS suggests a syndrome of the ovary, PCOS has also been associated with the central nervous system and other organ systems in the body due to the wide variety of symptoms it presents.

Methods

Here, we examined the expression patterns of PCOS candidate genes in gonadal (ovary and testis), metabolic (heart, liver and kidney) and brain (brain and cerebellum) tissues during the first half of human fetal development and postnatally until adulthood using public RNA sequencing data. This study is an initial step for more comprehensive and translational studies to define PCOS.

Results

We found that the genes were dynamically expressed in the fetal tissues studied. Some genes were significantly expressed in gonadal tissues, whilst others were expressed in metabolic or brain tissues at different time points prenatally and/or postnatally. HMGA2, FBN3 and TOX3 were highly expressed during the early stages of fetal development in all tissues but least during adulthood. Interestingly, correlation between expression of HMGA2/YAP1 and RAD50/YAP1 were significant in at least 5 of the 7 fetal tissues studied. Notably, DENND1A, THADA, MAPRE1, RAB5B, ARL14EP, KRR1, NEIL2 and RAD50 were dynamically expressed in all postnatal tissues studied.

Conclusions

These findings suggest that these genes have tissue- or development-specific roles in multiple organs, possibly resulting in the various symptoms associated with PCOS. Thus the fetal origin of a predisposition to PCOS in adulthood could arise via the effects of PCOS candidate genes in the development of multiple organs.
Associations between urinary iodine concentration and the prevalence of metabolic disorders: a cross-sectional study
Authors: Shen Xia , Yang Long , Liu Yuan-Yuan , Zhang Xue-He , Cai Ping , Huang Jian-Feng , Jiang Lei
Published: May 2023

Background

Few studies have examined the role of iodine in extrathyroidal function. Recent research has shown an association between iodine and metabolic syndromes (MetS) in Chinese and Korean populations, but the link in the American participants remains unknown.

Purpose

This study aimed to examine the relationship between iodine status and metabolic disorders, including components associated with metabolic syndrome, hypertension, hyperglycemia, central obesity, triglyceride abnormalities, and low HDL.

Methods

The study included 11,545 adults aged ≥ 18 years from the US National Health and Nutrition Examination Survey (2007–2018). Participants were divided into four groups based on their iodine nutritional status(ug/L), as recommended by the World Health Organization: low UIC, < 100; normal UIC, 100-299; high UIC, 300-399; and very high, ≥ 400. The Odds ratio (OR) for MetS basing the UIC group was estimated using logistic regression models for our overall population and subgroups.

Results

Iodine status was positively associated with the prevalence of MetS in US adults. The risk of MetS was significantly higher in those with high UIC than in those with normal UIC [OR: 1.25; 95% confidence intervals (CI),1.016-1.539; p = 0.035). The risk of MetS was lower in the low UIC group (OR,0.82; 95% CI: 0.708-0.946; p = 0.007). There was a significant nonlinear trend between UIC and the risk of MetS, diabetes, and obesity in overall participants. Participants with high UIC had significantly increased TG elevation (OR, 1.24; 95% CI: 1.002-1.533; P = 0.048) and participants with very high UIC had significantly decreased risk of diabetes (OR, 0.83; 95% CI: 0.731-0.945, p = 0.005). Moreover, subgroup analysis revealed an interaction between UIC and MetS in participants aged < 60 years and ≥ 60 years, and no association between UIC and MetS in older participants aged ≥ 60 years.

Conclusion

Our study validated the relationship between UIC and MetS and their components in US adults. This association may provide further dietary control strategies for the management of patients with metabolic disorders.
Effects of acromegaly treatment on left ventricular systolic function assessed by speckle tracking echocardiography in relation to sex differences: results from a prospective single center study
Authors: Popielarz-Grygalewicz Agata , Stelmachowska-Banaś Maria , Raczkiewicz Dorota , Czajka-Oraniec Izabella , Zieliński Grzegorz , Kochman Wacław , Dąbrowski Marek , Zgliczyński Wojciech
Published: May 2023

Background

Despite the preserved LVEF, patients with acromegaly are characterized by subclinical systolic dysfunction i.e., abnormal global longitudinal strain (GLS) assessed by speckle tracking echocardiography (STE). The effect of acromegaly treatment on LV systolic function assessed by STE, has not been evaluated so far.

Patients and methods

Thirty-two naïve acromegalic patients without detectable heart disease were enrolled in a prospective, single-center study. 2D-Echocardiography and STE were performed at diagnosis, 3&6 months on preoperative somatostatin receptor ligand (SRL) treatment and 3 months after transsphenoidal surgery (TSS).

Results

Treatment with SRL resulted in reduction in median (IQR) GH&IGF-1 levels after 3 months, from 9.1(3.2-21.9) to 1.8(0.9-5.2) ng/mL (p<0.001) and from 3.2(2.3-4.3) to 1.5(1.1-2.5) xULN (p<0.001), respectively. Biochemical control on SRL was achieved in 25.8% of patients after 6 months and complete surgical remission was achieved in 41.7% of patients. TSS resulted in decrease in median (IQR) IGF-1 compared to IGF-1 levels on SRL treatment: from 1.5(1.2-2.5) to 1.3(1.0-1.6) xULN (p=0.003). Females had lower IGF-1 levels at baseline, on SRL and after TSS compared to males. The median end diastolic and end systolic left ventricle volumes were normal. Almost half of the patients (46.9%) had increased LVMi, however the median value of LVMi was normal in both sex groups: 99g/m2 in males and 94g/m2 in females. Most patients (78.1%) had increased LAVi and the median value was 41.8mL/m2. At baseline 50% of patients, mostly men (62.5% vs. 37.5%) had GLS values higher than -20%. There was a positive correlation between baseline GLS and BMI r=0.446 (p=0.011) and BSA r=0.411 (p=0.019). The median GLS significantly improved after 3 months of SRL treatment compared to baseline: -20.4% vs. -20.0% (p=0.045). The median GLS was lower in patients with surgical remission compared to patients with elevated GH&IGF-1 levels: -22.5% vs. -19.8% (p=0.029). There was a positive correlation between GLS and IGF-1 levels after TSS r=0.570 (p=0.007).

Conclusion

The greatest beneficial effect of acromegaly treatment on LV systolic function is visible already after 3 months of preoperative SRL treatment, especially in women. Patients with surgical remission have better GLS compared to patients with persistent acromegaly.
New insights into signal transduction pathways in adrenal steroidogenesis: role of mitochondrial fusion, lipid mediators, and MAPK phosphatases
Authors: Mori Sequeiros Garcia María Mercedes , Paz Cristina , Castillo Ana Fernanda , Benzo Yanina , Belluno Matías A. , Balcázar Martínez Ariana , Maloberti Paula Mariana , Cornejo Maciel Fabiana , Poderoso Cecilia
Published: May 2023

Hormone-receptor signal transduction has been extensively studied in adrenal gland. Zona glomerulosa and fasciculata cells are responsible for glucocorticoid and mineralocorticoid synthesis by adrenocorticotropin (ACTH) and angiotensin II (Ang II) stimulation, respectively. Since the rate-limiting step in steroidogenesis occurs in the mitochondria, these organelles are key players in the process. The maintenance of functional mitochondria depends on mitochondrial dynamics, which involves at least two opposite events, i.e., mitochondrial fusion and fission. This review presents state-of-the-art data on the role of mitochondrial fusion proteins, such as mitofusin 2 (Mfn2) and optic atrophy 1 (OPA1), in Ang II-stimulated steroidogenesis in adrenocortical cells. Both proteins are upregulated by Ang II, and Mfn2 is strictly necessary for adrenal steroid synthesis. The signaling cascades of steroidogenic hormones involve an increase in several lipidic metabolites such as arachidonic acid (AA). In turn, AA metabolization renders several eicosanoids released to the extracellular medium able to bind membrane receptors. This report discusses OXER1, an oxoeicosanoid receptor which has recently arisen as a novel participant in adrenocortical hormone-stimulated steroidogenesis through its activation by AA-derived 5-oxo-ETE. This work also intends to broaden knowledge of phospho/dephosphorylation relevance in adrenocortical cells, particularly MAP kinase phosphatases (MKPs) role in steroidogenesis. At least three MKPs participate in steroid production and processes such as the cellular cycle, either directly or by means of MAP kinase regulation. To sum up, this review discusses the emerging role of mitochondrial fusion proteins, OXER1 and MKPs in the regulation of steroid synthesis in adrenal cortex cells.
Knowledge mapping of exosomes in metabolic diseases: a bibliometric analysis (2007-2022)
Authors: Xu Fangzhi , Xia Chenxi , Dou Lin , Huang Xiuqing
Published: May 2023

Background

Research on exosomes in metabolic diseases has been gaining attention, but a comprehensive and objective report on the current state of research is lacking. This study aimed to conduct a bibliometric analysis of publications on “exosomes in metabolic diseases” to analyze the current status and trends of research using visualization methods.

Methods

The web of science core collection was searched for publications on exosomes in metabolic diseases from 2007 to 2022. Three software packages, VOSviewer, CiteSpace, and R package “bibliometrix” were used for the bibliometric analysis.

Results

A total of 532 papers were analyzed, authored by 29,705 researchers from 46 countries/regions and 923 institutions, published in 310 academic journals. The number of publications related to exosomes in metabolic diseases is gradually increasing. China and the United States were the most productive countries, while Ciber Centro de Investigacion Biomedica en Red was the most active institution. The International Journal of Molecular Sciences published the most relevant studies, and Plos One received the most citations. Khalyfa, Abdelnaby published the most papers and Thery, C was the most cited. The ten most co-cited references were considered as the knowledge base. After analysis, the most common keywords were microRNAs, biomarkers, insulin resistance, expression, and obesity. Applying basic research related on exosomes in metabolic diseases to clinical diagnosis and treatment is a research hotspot and trend.

Conclusion

This study provides a comprehensive summary of research trends and developments in exosomes in metabolic diseases through bibliometrics. The information points out the research frontiers and hot directions in recent years and will provide a reference for researchers in this field.
Indocyanine green angiography-guided thyroidectomy versus conventional thyroidectomy for preserving parathyroid function: study protocol for a randomized single-blind controlled trial
Authors: Moreno-Llorente Pablo , García-González Guillermo , Pascua-Solé Mireia , García-Barrasa Arantxa , Videla Sebastián , Muñoz-de-Nova José Luis ,   the GuiArte Study Group
Published: May 2023

Introduction

Angiography with indocyanine green (ICG) fluorescence performed before thyroidectomy would allow identification of the vascularization of parathyroid glands, maximizing efforts for preserving functioning glands intraoperatively. The rationale of the study was based on the hypothesis that showing the vascular pattern of the parathyroid glands by means of ICG angiography before performing the thyroidectomy could prevent permanent hypoparathyroidism.

Methods and analysis

We propose a randomized single-blind controlled and multicenter clinical trial to assess the efficacy and safety of ICG angiography-guided thyroidectomy to identify the vascular pattern of the parathyroid glands versus conventional thyroidectomy in patients scheduled for elective total thyroidectomy. Patients will be randomized 1:1 to ICG angiography-guided thyroidectomy (experimental group) or conventional thyroidectomy (control group). Patients in the experimental group will undergo ICG angiography before thyroidectomy to identify the feeding vessels of the parathyroid glands and then, post-thyroidectomy ICG angiography to predict immediate parathyroid gland function by scoring the degree of fluorescence of the glands. Patients in the control group will undergo post-thyroidectomy ICG angiography only. The primary outcome measure will be the rate of patients with permanent hypoparathyroidism. Secondary outcome measures will be rate of postoperative hypoparathyroidism, the percentage of well vascularized parathyroid glands remaining in situ, the levels of iPTH and serum calcium after surgery and the influence of the type of vascular pattern of the parathyroid glands over these outcomes, as well as the safety profile of ICG angiography.

Discussion

The results will contribute to adopt a new surgical strategy based on intraoperative ICG angiography before performing total thyroidectomy, according to which the rate of permanent hypoparathyroidism could be substantially reduced.

Clinical trial registration

ClinicalTrials.gov. identifier NCT05573828.
Gut microbial profile of treatment-naive patients with primary biliary cholangitis
Authors: Zhou Yi-jun , Ying Gao-xiang , Dong Shi-lei , Xiang Bo , Jin Qiao-fei
Published: May 2023

Background and aims

The pathogenesis of primary biliary cholangitis (PBC) is associated with alterations of gut microbiota. We compared the gut microbiota of PBC patients and healthy controls from Zhejiang Province and assessed the use of these data for the diagnosis of PBC.

Methods

First, 16S rRNA gene sequencing was used to characterize the gut microbiota of treatment-naive PBC patients (n=25) and matched healthy controls (n=25). Then, the value of gut microbiota composition for the diagnosis of PBC and assessment of PBC severity was determined.

Results

The gut microbiota of PBC patients had lower diversity based on three different metrics of alpha-diversity (ace, Chao1, and observed features) and fewer overall genera (all p<0.01). PBC patients had significant enrichment of four genera and significant depletion of eight genera. We identified six amplicon sequence variants (Serratia, Oscillospirales, Ruminococcaceae, Faecalibacterium, Sutterellaceae, and Coprococcus) as optimal biomarkers to distinguish PBC patients from controls based on receiver operating characteristic analysis (area under the curve [AUC] = 0.824). PBC patients who were anti-gp210-positive had lower levels of Oscillospiraceae than those who were anti-gp210-negative. KEGG functional annotation suggested the major changes in the gut microbiota of PBC patients were related to lipid metabolism and biosynthesis of secondary metabolites.

Conclusion

We characterized the gut microbiota of treatment-naive PBC patients and healthy controls from Zhejiang Province. The PBC patients had significant alterations in their gut microbiota, suggesting that gut microbiota composition could be useful as a non-invasive tool for the diagnosis of PBC.
Case Report: ICIs-induced Guillain–Barré syndrome recovered from mycophenolate mofetil
Authors: Ding Mengge , Deng Chao , Liu Xianling , Jiang Shun , Gao Yuan , Fan Dan , Zhou Yiguang , He Jiangbo , Liu Chaoyuan
Published: May 2023

The emergence of immune checkpoint inhibitors (ICIs) has significantly prolonged the survival time of cancer patients. However, it may also lead to various immune-related adverse events (irAEs), including Guillain–Barré syndrome (GBS), a rare type of irAE. Most GBS patients can recover spontaneously due to the self-limited nature of the disease, but severe cases can result in respiratory failure or even death. Here we report a rare case of GBS occurring in a 58-year-old male patient with non-small cell lung cancer (NSCLC) who developed muscle weakness and numbness of the extremities during chemotherapy combined with KN046, a PD-L1/CTLA-4 bispecific antibody. Despite receiving methylprednisolone and γ-globulin, the patient’s symptoms did not improve. However, there was significant improvement after treatment with mycophenolate mofetil (MM) capsules, which is not a routine regimen for GBS. To the best of our knowledge, this is the first reported case of ICIs-induced GBS that responded well to mycophenolate mofetil instead of methylprednisolone or γ-globulin. Thus, it provides a new treatment option for patients with ICIs-induced GBS.
Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study
Authors: Ruan Zhe , Huan Xiao , Su Yue , Tang Yong-Lan , Meng Dong-Dong , Ren Da-Lin , Li Chun-Hong , Hao Si-Jia , Zhao Chong-Bo , Luo Su-Shan , Li Zhu-Yi , Chang Ting
Published: May 2023

Background

The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients.

Methods

The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression.

Results

Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination.

Conclusion

COVID-19 vaccination has no long-term impact on MG relapse.
Grouper RIP2 inhibits Singapore grouper iridovirus infection by modulating ASC-caspase-1 interaction
Authors: Zhang Xin , Wu Siting , Liu Zetian , Chen Hong , Liao Jiaming , Wei Jingguang , Qin Qiwei
Published: May 2023

Introduction

Receptor interacting protein 2 (RIP2), serves as a vital sensor of cell stress, is able to respond to cell survival or inflammation, and is involved in antiviral pathways. However, studies on the property of RIP2 in viral infections in fish have not been reported.

Methods

In this paper, we cloned and characterized RIP2 homolog from orange-spotted grouper (Epinephelus coioides) (EcRIP2) and further discussed the relevance of EcRIP2 to EcASC, comparing the influences of EcRIP2 and EcASC on the modulation of inflammatory factors and the NF-κB activation to reveal the mechanism of EcRIP2 in fish DNA virus infection.

Results

Encoded a 602 amino acid protein, EcRIP2 contained two structural domains: S-TKc and CARD. Subcellular localization signified that EcRIP2 existed in cytoplasmic filaments and dot aggregation patterns. After SGIV infection, the EcRIP2 filaments aggregated into larger clusters near the nucleus. The infection of SGIV could notably up-regulate the transcription level of the EcRIP2 gene compared with lipopolysaccharide (LPS) and red grouper nerve necrosis virus (RGNNV). Overexpression of EcRIP2 impeded SGIV replication. The elevated expression levels of inflammatory cytokines induced by SGIV were remarkably hindered by EcRIP2 treatment in a concentration-dependent manner. In contrast, EcASC treatment could up-regulate SGIV-induced cytokine expression in the presence of EcCaspase-1. Enhancing amounts of EcRIP2 could overcome the down regulatory effect of EcASC on NF-κB. Nevertheless, increasing doses of EcASC failed to restrain the NF-κB activation in the existence of EcRIP2. Subsequently, it was validated by a co-immunoprecipitation assay that EcRIP2 dose-dependently competed with EcASC binding to EcCaspase-1. With increasing time to SGIV infection, EcCaspase-1 gradually combined with more EcRIP2 than EcASC.

Discussion

Collectively, this paper highlighted that EcRIP2 may impede SGIV-induced hyperinflammation by competing with EcASC for binding EcCaspase-1, thereby suppressing viral replication of SGIV. Our work supplies novel viewpoints into the modulatory mechanism of RIP2-associated pathway and offers a novel view of RIP2-mediated fish diseases.
Isolation and identification of a novel toxin in scallop mantle tissue
Authors: Maeda Nabuki , Yoshida Fumika , Matsumoto Kota , Takahashi Saki , Xiong Geng , Hasegawa Yasushi
Published: May 2023

Scallops are one of the main marine products of Hokkaido, Japan. In addition to adductor muscle, scallop mantle tissue is often consumed in Japan. Previously, we showed that feeding mice a diet containing 1% mantle tissue resulted in lower food consumption and, ultimately, death. In this study, we isolated and identified toxic substances from scallop mantle tissue. The isolated toxic substances were protein complexes with molecular weights of 18 kDa and 29 kDa. Feeding mice a diet containing 0.05% toxic substances led to their death at five weeks. Based on LC-MS/MS analysis, the 29-kDa and 18-kDa proteins were identified as an actin fragment and the N-terminal fragment of the gelsolin-like protein, respectively. The 18-kDa protein was expressed in the mantle, gill, and ovary but not in the adductor muscle, testis, or midgland. Toxicity was observed only in mouse tissues expressing the 18-kDa protein. Feeding mice a diet containing only the 18-kDa protein did not induce decreased food consumption or death, implying that both the 29-kDa and 18-kDa complexes are essential for toxicity. This is the first study to identify a novel toxin in scallop tissues.
The role of androgen therapy in acquired aplastic anemia and other bone marrow failure syndromes
Authors: Nassani Momen , Fakih Riad El , Passweg Jakob , Cesaro Simone , Alzahrani Hazzaa , Alahmari Ali , Bonfim Carmem , Iftikhar Raheel , Albeihany Amal , Halkes Constantijn , Ahmed Syed Osman , Dufour Carlo , Aljurf Mahmoud
Published: May 2023

Bone marrow failure syndromes are a heterogeneous group of diseases. With the major advancements in diagnostic tools and sequencing techniques, these diseases may be better classified and therapies may be further tailored. Androgens, a historic group of drugs, were found to stimulate hematopoiesis by enhancing the responsiveness of progenitors. These agents have been used for decades to treat different forms of bone marrow failure. With the availability of more effective pathways to treat BMF, androgens are less used currently. Nevertheless, this group of drugs may serve BMF patients where standard therapy is contraindicated or not available. In this article, we review the published literature addressing the use of androgens in BMF patients and we make recommendations on how to best use this class of drugs within the current therapeutic landscape.