bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of Human Pituitary Neuroendocrine Tumor Derived Organoid and Its Pilot Application for Drug Screening
Authors: Cui Run , Duan Hao , Hu Wanming , Li Chang , Zhong Sheng , Liang Lun , Chen Siyu , Hu Hongrong , He Zhenqiang , Wang Zhenning , Guo Xiaoyu , Chen Zexin , Xu Cong , Zhu Yu , Chen Yinsheng , Sai Ke , Yang Qunying , Guo Chengcheng , Mou Yonggao , Jiang Xiaobing 
Published: April 2024

Abstract

Context
Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models.

Objective
To generate patient-derived organoids (PDOs), which could serve as a platform for personalized drug screening for PitNET patients.

Design
From July 2019 to May 2022, a total of 32 human PitNET specimens were collected for the establishment of organoids with an optimized culture protocol.

Setting
This study was conducted at Sun Yat-Sen University Cancer Center.

Patients
PitNET patients who were pathologically confirmed were enrolled in this study.

Interventions
Histological staining and whole-exome sequencing were utilized to confirm the pathologic and genomic features of PDOs. A drug response assay on PDOs was also performed.

Main Outcome Measures
PDOs retained key genetic and morphological features of their parental tumors.

Results
PDOs were successfully established from various types of PitNET samples with an overall success rate of 87.5%. Clinical nonfunctioning PitNETs-derived organoids (22/23, 95.7%) showed a higher likelihood of successful generation compared to those from functioning PitNETs (6/9, 66.7%). Preservation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histological, genomic, and microenvironment heterogeneity consistency assays, we demonstrated the predictive value of the PDOs in testing individual drugs.

Conclusion
The established PDOs, retaining typical features of parental tumors, indicate a translational significance in innovating personalized treatment for refractory PitNETs.
Prolonged disease control despite ALK inhibitor discontinuation in advanced ALK-positive NSCLC
Authors: Hussain Syed Ather , Faisal Hafsa , Dy Grace K. 
Published: April 2024

Introduction: EML4-ALK is an oncogenic driver, seen in around five per cent of advanced non-small-cell lung cancer (NSCLC) patients, which can be targeted with anaplastic lymphoma kinase tyrosine kinase inhibitors with great response rates. Disease flare refers to sudden rapid disease worsening on tyrosine kinase inhibitors (TKI) discontinuation, which is associated with shorter survival and worse outcomes. Here, we review cases previously published in the literature where patients developed disease flares, and contrast this with our patients who had prolonged survival despite TKI discontinuation. Case description: We report three different patients with advanced ALK-positive NSCLC seen at our institute, who had EML4-ALK translocation variant 1 oncogenic driver on next-generation sequencing. They received treatment with several different ALK inhibitors before opting to discontinue TKI. They were able to come off TKI safely without developing disease flare and had prolonged survival. Discussion: Shorter time to progression on TKI, presence of symptoms with disease progression or central nervous system/pleural metastasis have been previously linked with development of flare, although this was not seen in our case series. Tumour response at the time of treatment discontinuation, line of therapy, overall disease burden, fusion variant and co-alteration status can affect the prognosis of these patients after ALK TKI cessation. In particular, variant 1 and wild-type TP53 status may be a suitable patient population for dose optimisation strategies. Intermittent TKI dosing strategies may help to avoid acquiring resistance mutations and prevent long-term treatment toxicities. Conclusion: It is important for clinicians to identify patients at risk for developing disease flare on TKI discontinuation to improve outcomes. Intermittent TKI dosing strategies require further investigation.
Efficacy and safety of Yangxinshi tablet for chronic heart failure: A systematic review and meta-analysis
Authors: Lu Sheng-Hua , Yu Yun-Feng , Dai Si-Si , Hu Ya-Qi , Liu Jian-He 
Published: April 2024

BACKGROUND
The specific benefits of Yangxinshi tablet (YXST) in the treating chronic heart failure (CHF) remain uncertain.
AIM
To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.
METHODS
Randomized controlled trials (RCTs) investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023. Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.
RESULTS
Twenty RCTs and 1845 patients were included. The meta-analysis results showed that the YXST combination group, compared to the conventional drug group, significantly increased the clinical efficacy rate by 23% [relative risk (RR) = 1.23, 95%CI: 1.17-1.29], P < 0.00001), left ventricular ejection fraction by 6.69% [mean difference (MD) = 6.69, 95%CI: 4.42-8.95, P < 0.00001] and 6-min walk test by 49.82 m (MD = 49.82, 95%C: 38.84-60.80, P < 0.00001), and reduced N-terminal pro-B-type natriuretic peptide by 1.03 ng/L [standardized MD (SMD) = -1.03, 95%CI: -1.32 to -0.74, P < 0.00001], brain natriuretic peptide by 80.95 ng/L (MD = -80.95, 95%CI: -143.31 to -18.59, P = 0.01), left ventricular end-diastolic diameter by 3.92 mm (MD = -3.92, 95%CI: -5.06 to -2.78, P < 0.00001), and left ventricular end-systolic diameter by 4.34 mm (MD = -4.34, 95%CI: -6.22 to -2.47, P < 0.00001). Regarding safety, neither group reported any serious adverse events during treatment (RR = 0.54, 95%CI: 0.15-1.90, P = 0.33). In addition, Egger's test results indicated no significant publication bias (P = 0.557).
CONCLUSION
YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile, suggesting its potential as a therapeutic strategy for CHF.
Intra-thyroid esophageal duplication cyst: A case report
Authors: Lin Hong-Guo , Liu Ming , Huang Xue-Yang , Liu Da-Sheng 
Published: April 2024

BACKGROUND
Esophageal cysts are relatively rare in clinical practice, with most of the literature comprising case reports. Esophageal cysts protruding into the thyroid gland are easily misdiagnosed as thyroid tumors. No such cases have been reported so far.
CASE SUMMARY
This article reports the case of a 31-year-old adult male diagnosed with thyroid nodules before admission. The patient underwent left thyroidectomy and isthmusectomy. During the surgery, esophageal cysts were identified in the esophageal muscle and thyroid glands. The pathology results confirmed a nodular goiter combined with esophageal cysts. Postoperatively, the patient developed a neck infection and underwent another operation and broad-spectrum antibiotic treatment for recovery.
CONCLUSION
We report the first clinical case of an esophageal cyst located within the thyroid gland that was successfully treated surgically. Esophageal cyst located within the thyroid gland cause difficulties in diagnosis. In the present study, the contents of the esophageal cysts were calcified foci, and a small amount of fluid mixture, which were easily misdiagnosed as thyroid nodules and misled the surgical methods.
Thymic carcinoid with multiple bone metastases: A case report
Authors: Chen Chun-Qiao , Huang Ming-Yue , Pan Min , Chen Qiu-Qiu , Wei Fei-Fei , Huang Hui 
Published: April 2024

BACKGROUND
Thymic carcinoid (TC) is a rare entity among anterior mediastinal malignancies. TCs are neuroendocrine carcinomas that constitute approximately 2%–5% of all thymic epithelial tumors.
CASE SUMMARY
The study reported a rare TC with multiple bone metastases. A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg. Magnetic resonance imaging scans revealed damage to the lumbar spine, sacrocaudal vertebrae and iliac crest, suggesting bone metastasis; computed tomography (CT) scan of the thorax showed a calcified anterior mediastinal mass; positron emission tomography-CT demonstrated multiple abnormal bone signals; and laboratory work-up showed no endocrine abnormalities. Fine-needle aspiration biopsy revealed predominantly single small, round to oval cells with scant cytoplasm and some loose clusters, suggesting endocrine manifestations. The pathological diagnosis was atypical carcinoid, which tend to originate from the thymus and was classified as intermediate-highly invasive. The patient underwent anlotinib-targeted therapy. Anlotinib (12 mg) was administered daily for 2 wk, after which the patient was allowed to rest for 21 d. Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29% after therapy. Treatment has a long stable disease benefit of more than 2.5 years.
CONCLUSION
These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.
Who Demands Technical and Vocational Education in Pakistan? A PSLM Analysis of Socio-Economic Determinants
Authors: Khan Suhrab , Ali Kazim 
Published: April 2024

Purpose: The present study investigates the influence of demographic factors on the demand for Technical and Vocational Education and Training (TVET) in Pakistan. The government of Pakistan has implemented various skill enhancement programs to harness the demographic dividend. However, only a small portion of the workforce receives any form of TVET, contributing to a shortage of skilled workers in the country. Many industries, particularly in manufacturing and mining, face deficits in the skilled labour. Consequently, this study aims to examine the role of demographic factors in shaping the demand for TVET within the Pakistani context.
Methods: For the TVET demand's estimation, this study employed the Pakistan Social and Living Standard Measurement (PSLM) dataset of 2018–19 by using binary logistic regression analysis (BLRA). The demographic variables include the household's income, household head's education, household size, male proportion of the target age group, household head's age, and region of the household.
Findings: The findings indicate that households in the higher income category do not demand TVET. Moreover, if the head of the household is highly educated, then the household is less likely to participate in TEVT. So, the higher the socio-economic status, the lower the probability of demand for TVET from the better-off students. Further, this study also indicates that boys are more likely to participate in TVET-related degrees, while females are less likely to participate in TVET due to the non-availability of institutes and hostel facilities, poor transportation, the limited number of trades available for females, and security issues.
Conclusion: The findings provide insightful evidence to support the idea that the higher the socio-economic status of households, the lower the probability of demand for a TVET degree or diploma. Similarly, children of parents with university education are less likely to pursue TVET-related degrees. The reason is likely attributed to the perception that TVET-associated degrees and diplomas are considered inferior due to their lower standing and prestige as compared to general or professional degrees. This study suggests that the attractiveness of TVET can be enhanced by improving the quality of TVET, improving labour market outcomes, and creating a pathway to general education. Overall, this study not only contributes to empirical analyses of socio-economic determinants in TVET demand but also suggests that its findings can be applied not only to South Asian countries but also to other comparable nations with similar cultural ties and affinities.
How do social networks, perception of social isolation, and loneliness affect depressive symptoms among Japanese adults?
Authors: Kushibiki Natsuho , Aiba Miyuki , Midorikawa Haruhiko , Komura Kentaro , Sugawara Daichi , Shiratori Yuki , Kawakami Naoaki , Ogawa Takafumi , Yaguchi Chie , Tachikawa Hirokazu 
Published: April 2024

Objective
This study aims to elucidate the complex relationship among social isolation, loneliness, and perception of social isolation and its influence on depressive symptoms by evaluating a hypothetical model. This understanding is essential for the formulation of effective intervention strategies.

Methods
We conducted an online survey on Japanese adults (N = 3,315) and used the six-item Lubben Social Network Scale to assess the size of their social networks. We employed a single question to gauge their perception of social isolation. Loneliness was assessed using the three-item UCLA Loneliness Scale, and depressive symptoms were examined using the Patient Health Questionnaire-9. Structural equation modeling was employed to test the hypothesized model.

Results
The final model demonstrated satisfactory fit with data (χ2 (1) = 3.73; not significant; RMSEA = 0.03; CFI = 1.00; TLI = 1.00). The size of social network demonstrated a weak negative path to loneliness and depressive symptoms (β = −.13 to −.04). Notably, a strong positive association existed between perception of social isolation and loneliness (β = .66) and depressive symptoms (β = .27). Additionally, a significant positive relationship was found between loneliness and depressive symptoms (β = .40). Mediation analysis indicated that perception of social isolation and loneliness significantly intensified the relationships between social networks and depressive symptoms.

Conclusions
Results indicate that interventions of psychological approaches, such as cognitive–behavioral therapy, are effective in reducing the perception of social isolation and loneliness, which may lead to the prevention of depressive symptoms. Future longitudinal studies are expected to refine and strengthen the proposed model.
Brief report: Effect of cardiac multi-morbidity on COVID hospitalization outcomes
Authors: Chouairi Fouad , Jaffe Edward , Minhas Abdul Mannan Khan , Fudim Marat 
Published: April 2024

Background
The COVID-19 pandemic has stretched healthcare resources thin and led to significant morbidity and mortality. There have been no studies utilizing national data to investigate the role of cardiac risk factors on outcomes of COVID hospitalizations. The aim of this study was to examine the effect of cardiac multimorbidity on healthcare utilization and outcomes among COVID hospitalizations during the first year of the pandemic.

Methods
Using the national inpatient sample (NIS), we identified all adult hospital admissions with a primary diagnosis of COVID in 2020, using International Classification of Diseases, Tenth Revision, Clinical Modification codes (ICD010-CM). Coronary artery disease, diabetes mellitus, heart failure, peripheral vascular disease, previous stroke, and atrial fibrillation were then identified as cardiac comorbidities using ICD-10-CM codes. Multivariable logistic regression was used to evaluate the effect of cardiac multimorbidity on mortality and mechanical ventilation.

Results
We identified 1,005,040 primary COVID admissions in 2020. Of these admissions, 216,545 (20.6%) had CAD, 413,195 (39.4%) had DM, 176,780 (16.8%) had HF, 159,700 (15.2%) had AF, 30735 (2.9%) had PVD, and 25,155 (2.4%) had a previous stroke. When stratified by number of comorbidities, 428390 (40.8%) had 0 comorbidities, 354960 (33.8%) had 1, 161225 (15.4%) had 2, and 105465 (10.0%) had 3+ comorbidities. COVID hospitalizations with higher cardiac multimorbidity had higher mortality rates (p<0.001) higher MV rates (p<0.001). In our multivariable regression, these associations remained with increasing odds for mortality with each stepwise increase in cardiac multimorbidity (1: OR 1.48 (1.45–1.50); 2: OR 2.13 (2.09–2.17); 3+: OR 2.43 (2.38–2.48), p<0.001, all).

Conclusions
Our study is the first national examination of the impact of cardiac comorbidities on COVID outcomes. A higher number of cardiac comorbidities was associated with significantly higher rates of MV and in-hospital mortality, independent of age. Future, more granular, and longitudinal studies are needed to further examine these associations.
Development and validation of a nomogram for predicting 28-day mortality in patients with ischemic stroke
Authors: Fang Lingyan , Zhou Menglu , Mao Fengkai , Diao Mengyuan , Hu Wei , Jin Guangyong 
Published: April 2024

Background/aim
We aimed to construct a validated nomogram model for predicting short-term (28-day) ischemic stroke mortality among critically ill populations.

Materials and methods
We collected raw data from the Medical Information Mart for Intensive Care IV database, a comprehensive repository renowned for its depth and breadth in critical care information. Subsequently, a rigorous analytical framework was employed, incorporating a 10-fold cross-validation procedure to ensure robustness and reliability. Leveraging advanced statistical methodologies, specifically the least absolute shrinkage and selection operator regression, variables pertinent to 28-day mortality in ischemic stroke were meticulously screened. Next, binary logistic regression was utilized to establish nomogram, then applied concordance index to evaluate discrimination of the prediction models. Predictive performance of the nomogram was assessed by integrated discrimination improvement (IDI) and net reclassification index (NRI). Additionally, we generated calibration curves to assess calibrating ability. Finally, we evaluated the nomogram’s net clinical benefit using decision curve analysis (DCA), in comparison with scoring systems clinically applied under common conditions.

Results
A total of 2089 individuals were identified and assigned into training (n = 1443) or validation (n = 646) cohorts. Various identified risk factors, including age, ethnicity, marital status, underlying metastatic solid tumor, Charlson comorbidity index, heart rate, Glasgow coma scale, glucose concentrations, white blood cells, sodium concentrations, potassium concentrations, mechanical ventilation, use of heparin and mannitol, were associated with short-term (28-day) mortality in ischemic stroke individuals. A concordance index of 0.834 was obtained in the training dataset, indicating that our nomogram had good discriminating ability. Results of IDI and NRI in both cohorts proved that our nomogram had positive improvement of predictive performance, compared to other scoring systems. The actual and predicted incidence of mortality showed favorable concordance on calibration curves (P > 0.05). DCA curves revealed that, compared with scoring systems clinically used under common conditions, the constructed nomogram yielded a greater net clinical benefit.

Conclusions
Utilizing a comprehensive array of fourteen readily accessible variables, a prognostic nomogram was meticulously formulated and rigorously validated to provide precise prognostication of short-term mortality within the ischemic stroke cohort.
Educação Musical como campo científico
Authors: Souza Jusamara 
Published: April 2024

A pesquisa em Educação Musical no Brasil vem se estabelecendo, desde a década de 1990, graças à criação de associações, cursos e programas de pós-graduação e à realização de eventos e publicações na área específica. Para se fazer pesquisa em Educação Musical é necessário ter clareza da área como um campo capaz de produzir novos conhecimentos, dividindo, assim, as mesmas preocupações com outras ciências. O presente ensaio discute a epistemologia da Educação Musical, abordando as particularidades do conhecimento pedagógico-musical, a construção do objeto da área, aspectos históricos da discussão deste tema e contribuições recentes sobre a cientificidade da área. Construir o campo da Educação Musical significa criar uma disciplina científica autônoma, que possa dialogar com outros campos, como qualquer outra área do conhecimento o faz.
uso de personagens sob a forma de bonecos como recurso para criação de vínculos afetivos nas aulas de artes visuais para Educação Infantil e Ensino Fundamental Anos Iniciais
Authors: Rodrigues Sérgio 
Published: April 2024

O texto relata práticas educativas em artes visuais realizadas entre 2010 e 2019, nas quais o uso de personagens na forma de bonecos de pano foi um recurso para construir e fortalecer vínculos afetivos com os conteúdos artísticos, gerando experiências significativas para crianças na Educação Infantil e no Ensino Fundamental Anos Iniciais. Nisto, procuramos enfatizar como a preparação de contextos lúdicos de aprendizagem mediados por bonecos permitiu a presença da Arte no ambiente escolar de forma mais ampla e promoveu a criação de espaços expositivos e experimentais para a produção e mostra dos alunos, bem como exposições com reproduções de obras de arte.
responsabilidade da prática docente no deslocamento sudeste-nordeste
Authors: Pavão Pampuri Mendes Violeta 
Published: April 2024

O presente ensio analisa a prática docente de profissionais que se deslocam do sudeste para o nordeste do Brasil, para lecionar em universidades interiorizadas do Ensino Superior. A autora compreende que este deslocamento vem carregado de práticas coloniais refletidas em conflitos em sala de aula. A pesquisa se dá através do deslocamento da autora, que sai do Rio de Janeiro (RJ) em 2018 e passa a lecionar no ensino superior no estado da Bahia, passando da Mesorregião do Vale São-Franciscano para a Mesorregião do Extremo Oeste Baiano. As reflexões são potencializadas a partir dos pensamentos de Jota Mombaça (RN), Leda Maria Martins (MG) e Luiz Rufino Rodrigues Junior (RJ), entre outras pessoas artistas-teóricas, com as quais é possível aprofundar investigações sobre reparação histórica, tensionamentos de fronteiras, práticas pedagógicas decoloniais, entre outros pontos relevantes para este trabalho que levam em conta fatores sociais, econômicos, culturais, e históricos que formam as academias do sudeste e nordeste. A partir desses pontos, o artigo tem como objetivo apontar caminhos para práticas pedagógicas contextualizadas com os processos históricos de formação social do Brasil e em relação saudável com os territórios das universidades interiorizadas.
PALAVRAS-CHAVE: Deslocamento. Educação Decolonial. Docência. Prática Pedagógica. Ensino Superior.
Necessidades e suporte familiar
Authors: Muniz Joice Daiane , Cia Fabiana 
Published: April 2024

Esta pesquisa teve por objetivos: identificar e analisar as necessidades e o suporte social das famílias de crianças e adolescentes de seis a quatorze anos com síndrome de Down e relacionar essas variáveis. Participaram da pesquisa 11 mães/ responsáveis por crianças e adolescentes com síndrome de Down. Os instrumentos utilizados foram aplicados em forma de entrevistas, sendo: Questionário sobre as necessidades das famílias, Questionário de Suporte Social e Inventário de Recursos do Ambiente familiar. Os dados foram analisados usando métodos descritivos. Para relacionar as variáveis, foi utilizado o teste de correlação de Pearson. Os resultados mostraram que as maiores necessidades das famílias estavam relacionadas ao apoio e às informações de que o filho poderia se beneficiar no futuro e sobre o desenvolvimento deles. Em relação ao suporte social, as famílias se mostraram suportivas a diversas situações. Quanto às correlações têm-se que quanto maior a idade das mães, maior as necessidades de serviços na comunidade; quanto maior a idade das crianças, menor as necessidades de informações das famílias e quanto maior as necessidades de explicar aos outros, as necessidades de serviços na comunidade, as necessidades da vida familiar e necessidades totais, maior a satisfação com o suporte social das mães.