bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID lockdown on glycaemic control in paediatric patients with type 1 diabetes: A systematic review and meta-analysis of 22 observational studies
Authors: Han Yanping , Chen Yuqing , Sun Chenyu , Zhou Zhen 
Published: November 2022

IntroductionThe COVID lockdown has posted a great challenge to paediatric patients with type 1 diabetes (T1D) and their caregivers on the disease management. This systematic review and meta-analysis sought to compare the glycaemic control among paediatric patients with T1D (aged under 18 years) pre- during, and post-lockdown period.Methods and materialsWe did a systematic search of three databases (PubMed, Embase, and the WHO COVID‐19 Global literature) for the literature published between 1 Jan 2019 to 10 Sep 2022. Studies meeting the following inclusion criteria were eligible for this study: (1) a COVID-19 related study; (2) inclusion of children aged 18 years old or under with established T1D; (3) comparing the outcomes of interest during or after the COVID lockdown with that before the lockdown. Study endpoints included mean difference (MD) in HbA1c, blood glucose, time in range (TIR, 70-180 mg/dl), time above range (TAR, &gt;180mg/dl), time below range (TBR,&lt;70mg/dl) and glucose variability (coefficient of variation [CV]) between pre-lockdown and during lockdown and/or between pre- and post-lockdown period. The MD and its corresponding 95% CI of each endpoint were pooled using random-effect model considering the potential between-study heterogeneity in COVID restrictions and T1D management.ResultsInitial search identified 4488 records and 22 studies with 2106 paediatric patients with T1D were included in the final analysis. Compared with pre-lockdown period, blood glucose was significantly decreased by 0.11 mmol/L (95%CI: -0.18, -0.04) during lockdown period and by 0.42 mmol/L (95%CI: -0.73, -0.11) after lockdown. The improvement was also found for TIR, TAR, TBR, and CV during and post-lockdown (all p values&lt;0.05) except for the post-lockdown TBR (p =0.35). No significant change in HbA1c was observed during and post- lockdown period when compared with the pre-lockdown value. There was moderate to high between-study heterogeneity for most of the analyses.ConclusionCompared with pre-lockdown period, there was significant improvement in T1D paediatric patients’ glucose metrics during and post-lockdown. The underlying reasons for this positive impact warrant further investigation to inform future paediatric diabetes management.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022359213.
Integrating cell interaction with transcription factors to obtain a robust gene panel for prognostic prediction and therapies in cholangiocarcinoma
Authors: Wang Tingjie , Xu Chuanrui , Xu Dan , Yang Xiaofei , Liu Yaxin , Li Xiujuan , Li Zihang , Dang Ningxin , Lv Yi , Zhang Zhijing , Li Lei , Ye Kai 
Published: November 2022

Objective: The efficacy of immunotherapy for cholangiocarcinoma (CCA) is blocked by a high degree of tumor heterogeneity. Cell communication contributes to heterogeneity in the tumor microenvironment. This study aimed to explore critical cell signaling and biomarkers induced via cell communication during immune exhaustion in CCA.Methods: We constructed empirical Bayes and Markov random field models eLBP to determine transcription factors, interacting genes, and associated signaling pathways involved in cell-cell communication using single-cell RNAseq data. We then analyzed the mechanism of immune exhaustion during CCA progression.Results: We found that VEGFA-positive macrophages with high levels of LGALS9 could interact with HAVCR2 to promote the exhaustion of CD8+ T cells in CCA. Transcription factors SPI1 and IRF1 can upregulate the expression of LGALS9 in VEGFA-positive macrophages. Subsequently, we obtained a panel containing 54 genes through the model, which identified subtype S2 with high expression of immune checkpoint genes that are suitable for immunotherapy. Moreover, we found that patients with subtype S2 with a higher mutation ratio of MUC16 had immune-exhausted genes, such as HAVCR2 and TIGIT. Finally, we constructed a nine-gene eLBP-LASSO-COX risk model, which was designated the tumor microenvironment risk score (TMRS).Conclusion: Cell communication-related genes can be used as important markers for predicting patient prognosis and immunotherapy responses. The TMRS panel is a reliable tool for prognostic prediction and chemotherapeutic decision-making in CCA.
First insight into H3K4me3 modification in the rapid growth of Alexandrium pacificum (dinoflagellates)
Authors: Qi Juan , Zhu Zhimei , Liu Yuan , Sui Zhenghong 
Published: November 2022

BackgroundAlexandrium pacificum is a dinoflagellate species notorious for its rapid growth resulting in large-scale blooms. This study aimed to investigate the molecular mechanisms of A. pacificum under laboratory-simulated rapid growth conditions from the perspective of H3K4me3 modification regulation.Methods and resultsWestern blot was used to detect the modification abundance of H3K4me3 in A. pacificum cultured under different conditions, including high light (HL), high nitrogen (HN), and f/2 medium (control, CT), in the rapid growth exponential phase. The results showed that the modification abundance of H3K4me3 under HL or HN was greater than that under CT. Chromatin immunoprecipitation-sequencing was used to explore the acting genes of H3K4me3 under different conditions for the first time. Nitrogen metabolism and endocytosis were significantly associated with H3K4me3 regulation under HL. Furthermore, H3K4me3 was also significantly associated with the vitamin metabolism pathway under HN.ConclusionsThese findings demonstrate that H3K4me3 plays a potentially important role in the regulation of the rapid growth of A. pacificum. Such knowledge of a histone modification regulatory network in this dinoflagellate, lays a necessary foundation for future research in related fields.
Kaempferol attenuated diabetic nephropathy by reducing apoptosis and promoting autophagy through AMPK/mTOR pathways
Authors: Sheng Hongqin , Zhang Duo , Zhang Jiaqi , Zhang Yanmei , Lu Zhaoyu , Mao Wei , Liu Xusheng , Zhang Lei 
Published: November 2022

IntroductionRenal podocyte injury, apoptosis and autophagy are involved in the occurrence and development of diabetic nephropathy (DN). Kaempferol (KPF) has the promotion of autophagy and inhibition of apoptosis properties in the development of miscellaneous diseases, but these functions in DN have not yet been elucidated.MethodsWe used db/db mice to evaluate the protective role of KPF on DN. The anti-DN effect of KPF was evaluated by urine albumin-to-creatinine ratio and pathological changes of kidney tissue. Injury of podocytes was observed through Transmission electron microscopy. Immunofluorescence, Western blot, and Immunohistochemistry were used to detect the protein expression of podocyte-associated molecules, autophagy, and AMPK/mTOR pathway.ResultsWe demonstrated that KPF treatment significantly attenuated diabetes-induced albuminuria and glycolipid metabolism dysfunction. In addition, KPF alleviated mesangial matrix expansion, glomerular basement membrane thickening and loss or fusion of podocytes. Mechanistically, KPF treatment regulated the expression of autophagic proteins (upregulated LC3II, Beclin-1, Atg7 and Atg 5, and downregulated p62/SQSTM1), accompanied by inhibited renal apoptosis (downregulated Caspase 3 and Bax, and upregulated Bcl-2). KPF could significantly regulate the AMPK/mTOR signaling pathways by increasing p-AMPK and decreasing p-mTOR expressions.DiscussionIn conclusion, KPF might have a protective effect on DN through reduced apoptosis and enhanced podocytes autophagy, which were correlated with regulating AMPK/mTOR pathways.
Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
Authors: Zeng Jing , Sun Lu , Huang Jiaming , Yang Xia , Hu Wanming 
Published: November 2022

BackgroundEnhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma is a poor prognostic factor, but the research of EZH2 in meningioma is rare. Therefore, we aim to explore the expression of EZH2 in the meningioma and its correlation with the prognosis and immune microenvironment and lay the foundation for the subsequently potential targeted therapy and immunotherapy for meningioma.MethodsTissue microarray immunohistochemistry staining was performed on 276 meningioma samples from Sun Yat-sen University Cancer Center. Expression levels of EZH2, H3K27me3, Ki67, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), CD4, CD8, CD20, FOXP3, CD68, and CD163 were evaluated. Cox regression analyses were performed, and the Kaplan–Meier (KM) method was used to construct survival curves. In addition, we use biological information methods to analyze the mRNA expression of EZH2 and its relationship with the prognosis and immune microenvironment in the gene expression omnibus (GEO) database.ResultsEnhancer of zeste homolog 2 expression is concentrated in World Health Organization (WHO) grades 2 and 3 meningiomas (8.3+ and 33.3%+). We found that EZH2 expression was associated with a worse prognosis in meningioma (P &lt; 0.001), the same results were confirmed in the GEO database (P &lt; 0.001). Both EZH2 expression and H3K27me3 deletion (P = 0.035) predicted a worse prognosis, but EZH2 has no correlation with H3K27me3 expression. EZH2 expression was closely associated with increased Ki67 index (P &lt; 0.001). In addition, EZH2 was associated with the immune microenvironment and positively correlated with PD-L1 expression (P &lt; 0.001).ConclusionEnhancer of zeste homolog 2 is a new prognostic biomarker in meningioma. It correlates with PD-L1 expression and closely related to tumor immunosuppression. Our research can provide a reference for the potential targeted therapy and immunotherapy of meningioma in the future.
The combination of a seven-autoantibody panel with computed tomography scanning can enhance the diagnostic efficiency of non-small cell lung cancer
Authors: He Tianyu , Wu Ziheng , Xia Pinghui , Wang Weidong , Sun Hua , Yu Li , Lv Wang , Hu Jian 
Published: November 2022

BackgroundNon-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC.MethodsWe retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel.ResultsThe strategy of a “both-positive rule” combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P&lt;0.05). The nomogram we established has passed the calibration test (P=0.987&gt;0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (P&lt;0.001), lower pathological differentiation degrees (P=0.018), more advanced pathological stages (P=0.040) and higher Ki-67 indexes (P=0.011) in patients with adenocarcinoma.ConclusionThis study shows that combination of a 7-AAB panel with CT has can significantly enhance the diagnostic efficiency of lung cancer. Moreover, the 7-AAB panel also has potential prognostic value and has reference significance for the formulation of the treatment plan.
Unmet supportive care needs and associated factors: Evidence from 4195 cancer survivors in Shanghai, China
Authors: Chen Minxing , Li Ruijia , Chen Yujie , Ding Gang , Song Jie , Hu Xiaojing , Jin Chunlin 
Published: November 2022

BackgroundCancer survivors at different stages of life often have different needs that make it challenging for services to provide satisfactory care. Few studies have considered whether services are truly meeting the needs of cancer patients by exploring and identifying their perspectives on unmet needs.ObjectiveThe aim of this study was to identify the unmet needs of cancer survivors and to further determine the potential impact of socio-demographic factors.MethodsA cross-sectional study that included 4195 cancer patients was conducted in Shanghai, China. Using Maslow’s hierarchy of needs theory as a conceptual framework, the questionnaire included five dimensions: information, life and finances, continuing care, emotions, and self-actualization. Correlation analysis and ordered logistic regression analysis was used to explore the relationship between demographic sociological factors and unmet needs for supportive care.ResultsThe most common unmet supportive care needs include information needs (2.91 ± 1.32), self-actualization needs (2.69 ± 1.32) and continuing care needs (2.59 ± 1.30). Unmet needs for life and finances were more pronounced among cancer participants in the 45-69 age group. After adjusting for confounders, we found that each 6-month increase in the time since diagnosis was associated with a 0.8% (OR: 0.992, 95% CI: 0.985-0.998) reduction in high need for continuing care and a 0.9% (OR:0.991, 95% CI: 0.983-0.999) reduction in high need for self-actualization, respectively.ConclusionsInformation needs are the most important concern among the diverse unmet needs of cancer survivors. Time since diagnosis is associated with unmet supportive care needs of cancer survivors. The findings highlight the large gap between actual health services and patients’ unmet need for supportive care, which will provide the basis for a patient-centered supportive care system for cancer survivors.
Pan-Cancer analysis shows that ACO2 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including hepatocellular carcinoma
Authors: Wang Zhen , Zheng Wanqun , Chen Zhen , Wu Shilun , Chang Haoxiao , Cai Ming , Cai Heping 
Published: November 2022

BackgroundRecent evidence increasingly suggests key roles for the tricarboxylic acid cycle and fatty acid metabolism in tumor progression and metastasis. Aconitase 2 (ACO2) is a component of the tricarboxylic acid cycle and represents a key cellular metabolic hub that promotes de novo fatty acid biosynthesis. However, there have been few reports on the role of ACO2 in tumorigenesis and cancer progression.MethodsThrough the comprehensive use of datasets from The Cancer Genome Atlas, Genotype-Tissue Expression Project, cBioPortal, Human Protein Atlas, UALCAN, Gene Expression Profiling Interactive Analysis, DNA Methylation Interactive Visualization Database, and TIMER2, we adopted bioinformatics methods to uncover the potential carcinogenic roles of ACO2, including by analysing ACO2 expression and correlations between prognosis, genetic mutations, immune cell infiltration, DNA methylation, tumor mutational burden, and microsatellite instability in different tumors. Additionally, the expression level and tumor-promoting effect of ACO2 were verified in hepatocellular carcinoma (HCC) cells. To explore the underlying mechanisms of ACO2 in human cancer, ACO2-related gene enrichment analysis and lipid metabolomics were performed using LM3 cells with or without ACO2 knockdown.ResultsThe results indicated that ACO2 was highly expressed in most cancers, showing early diagnostic value in six tumor types, and was positively or negatively associated with prognosis in different tumors. Moreover, ACO2 expression was associated with immune cell infiltration, such as CD8+ T cells and tumor-associated neutrophils, in some cancers. For most cancer types, there was a significant association between immune checkpoint-associated genes and ACO2 expression. Compared with normal hepatocytes, ACO2 was upregulated in HCC cells, which promoted their proliferation and migration. Furthermore, to explore the underlying molecular mechanism, we performed KEGG pathway enrichment analysis of ACO2-associated genes and lipidomics using LM3 cells with or without ACO2 knockdown, which screened 19 significantly altered metabolites, including 17 with reduced levels and 2 with increased levels.ConclusionThrough pan-cancer analysis, we discovered for the first time and verified that ACO2 could be a useful diagnostic biomarker for cancer detection. Additionally, ACO2 could be used as an auxiliary prognostic marker or as a marker for immunotherapy in some tumor types.
The effect of swaddling on infant sleep and arousal: A systematic review and narrative synthesis
Authors: Dixley Allison , Ball Helen L. 
Published: November 2022

BackgroundWestern parents swaddle infants to promote sleep and reduce night-waking, however recent evidence of the effects of swaddling on the sleep of healthy infants has not been systematically reviewed.ObjectiveTo investigate the effect of swaddling on the sleep of infants up to 1 year of age using a narrative synthesis approach.Data SourcesWe systematically searched five academic databases, including the Cochrane trial registry (Pubmed, PsycINFO, Embase, the Cochrane library, and Blackwell Synergy). We manually searched reference lists and citations of included studies and reference lists of existing reviews.Study SelectionStudies of any type, published since 2007, reporting primary data whose subjects were humans up to 12 months of age with outcome measures relating to the impact of swaddling on sleep and arousal.Data ExtractionBy hand using a customized template. A narrative synthesis is used to present the results.ResultsIn total 171 studies were retrieved with 115 studies discarded at title. A further 43 were discarded at abstract, and six were discarded at full text. Two papers were combined as they reported on the same study giving a total of 6 studies that met the inclusion criteria for the review. An evidence hierarchy was used to assess Risk of Bias in the included studies; the results are presented via a narrative synthesis. Swaddling was associated with increased duration of quiet sleep in infants and a significantly reduced number of sleep state changes among infants naïve to the intervention.LimitationsThe integrity of the intervention (swaddling) including its baseline characteristics, was defined broadly across the included studies limiting the interpretation and transferability of the results of this review.ConclusionsSwaddling appears to increase quiet sleep duration in infants and reduces the number of sleep state changes among infants naïve to the intervention. Parents should be made aware that implementing conditions unfavorable to arousability may increase SUDI risk among infant who have not previously been swaddled. This review has relevance for informing future practice recommendations and parent advice as well as in designing future studies.
Incidence of central precocious puberty more than doubled during COVID-19 pandemic: Single-center retrospective review in the United States
Authors: Trujillo Marcela Vargas , Rungvivatjarus Tiranun , Klein Karen O. 
Published: November 2022

Background and aim of the studyThe frequency of new visits for precocious puberty increased during the Covid-19 pandemic in the pediatric endocrinology clinic at Rady Children's Hospital in San Diego, CA, US. A few recent studies have shown an increase in the frequency of Central Precocious Puberty (CPP) in other centers during this pandemic. This study evaluated the change in incidence of new CPP cases requiring treatment with GnRH agonist (GnRHa) at Rady Children's Hospital during the Covid-19 pandemic and compared it to pre-pandemic years.MethodsData were reviewed retrospectively to compare the number of visits of children newly diagnosed with CPP treated with GnRHa during the Covid-19 pandemic (5/2020–4/2021) and before the pandemic (5/2018–4/2019). Clinical and bone maturation data were evaluated as well as differences in timing from diagnosis to onset of treatment. The incidence of CPP requiring treatment for 5 years prior to the pandemic was also reviewed to evaluate for trends over time.ResultsA total of 92 subjects were included. During pre-Covid year, 28 children (1 boy, 27 girls) were treated with GnRHa for CPP out of 2,340 new endocrinology visits (1.2% of patients seen). During Covid-19 year, 64 children (7 boys, 57 girls) were treated out of 2,261 new visits (2.8%). The incidence of new CPP cases requiring GnRHa during the pandemic more than doubled compared to pre-pandemic. Age at onset of treatment, degree of bone age (BA) advancement, time from diagnosis to onset of treatment, and changes in BMI during the pandemic were not different from pre-pandemic.ConclusionCPP cases requiring GnRHa treatment significantly increased during the first year of the Covid-19 pandemic. This was not related to increased BMI or delay in onset of treatment. Age at diagnosis, degree of bone age advancement, and time from diagnosis to onset of treatment were all similar during the first year of the pandemic compared to the prior year.
Molecular and hematological studies in a cohort of beta zero South East Asia deletion (β°-thal SEA) from Malaysian perspective
Authors: Yasin Norafiza Mohd , Abdul Hamid Faidatul Syazlin , Hassan Syahzuwan , Sudin Aziee , Yassim Haiyuni , Mohd Sahid Ermi Neiza , Mat Yusoff Yuslina , Esa Ezalia , Saleem Mohamed 
Published: November 2022

AbstractWe report the haematological parameters and molecular characterization of beta zero (β°) South East Asia (SEA) deletion in the HBB gene cluster with unusually high levels of Hb F compared to a classical heterozygous beta zero (β°)-thalassaemia.MethodsRetrospective study on 17 cases of (β°) South East Asia (SEA) deletion from 2016 to 2019 referred to Institute for Medical Research were conducted. The clinical information and haematological profiles were evaluated. The mutation was analyzed, and the results were compared with other β°-thalassaemia groups. For HBB gene genotyping, all the cases were subjected for multiplex gap-PCR, 5 cases were subjected for HBB gene sequencing for exclusion of compound heterozygous with other beta variants. Co-inheritance of α-thalassaemia were determined using multiplex gap-PCR and multiplex ARMS-PCR.ResultsSeventeen cases were positive for β°-thal SEA deletion. Fifteen cases were heterozygous and two were compound heterozygous for β°-thal SEA deletion. The results were compared with 182 cases of various heterozygous β° deletions and mutations. The mean Hb for heterozygous β°-thal SEA deletion (13.44 ± 1.45 g/dl) was normal and significantly higher than heterozygous IVS 1-1 and Codon 41/42 (post hoc test, p &lt; 0.05). The medians for the MCV and MCH of β°-thal SEA deletion were significantly higher than for all heterozygote β°-thalassaemia traits (Mann Whitney test, p &lt; 0.05). Patients with β°-thal SEA deletion had elevated levels of Hb A2 consistent with β-thalassaemia traits, with Hb F levels consistent with HPFH or δβ-thalassaemia carriers. The median for Hb A2 was 4.00 + 1.00%, similar to that observed in other β°-thalassaemia groups except for IVS 1-1 mutation (median 5.30 + 0.45%) and β°-Filipino (∼45 kb deletion) deletion (median 6.00 + 0.58). Interestingly, we found that Hb F levels for β°-thal SEA deletion were statistically higher than other β°-thalassaemia mutations (median 19.00 + 5.50%, p &lt; 0.05), except for the β°-thal 3.5 kb deletion group.ConclusionWe conclude that β°-thal SEA deletion has a unique haematological parameters of beta zero thalassaemia trait. We affirm to classifying this deletion as SEA-HPFH based on previous studies considering the phenotype features rather than the molecular defect of β°-thal SEA deletion, as this will make it easier to offer genetic counselling to affected individuals.