bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortisol and Phosphate Homeostasis: Cushing’s Syndrome Is Associated With Reversible Hypophosphatemia
Authors: Bosman Ariadne , van den Beld Annewieke W. , Feelders Richard A. , Zillikens M. Carola 
Published: October 2021

ObjectivesThe influence of hypercortisolism on phosphate homeostasis is relatively unknown. A few previous studies have reported on patients with Cushing’s syndrome (CS) with hypophosphatemia in whom serum phosphate normalized after initiation of treatment for CS. We aimed to investigate the prevalence of hypophosphatemia in CS, the association between the degree of hypercortisolism and serum phosphate and the change in serum phosphate after remission of CS. We compared the prevalence of hypophosphatemia in CS with the prevalence in the population-based Rotterdam Study (RS).MethodsPatients diagnosed with CS and treated at the Department of Endocrinology of Erasmus MC in the period of 2002-2020 were included and data was collected on age at diagnosis, sex, serum phosphate, calcium and potassium levels, kidney function and BMI. Using multivariate linear regression, we analyzed the association between 24h urinary free cortisol excretion (UFC) and serum phosphate. Changes in serum phosphate and covariates were tested with a repeated measurement ANOVA, using mean levels of laboratory values for the periods before remission, and 0-14 days and 15-180 days after remission.ResultsHypophosphatemia before treatment was present in 16% of the 99 CS patients with data on serum phosphate, 24h UFC and covariates. In comparison, the prevalence of hypophosphatemia in RS was 2.0-4.2%. Linear regression showed a negative association between the level of UFC and serum phosphate at diagnosis, which remained significant after adjusting for covariates [β -0.002 (95%CI -0.004; -0.0004), p=0.021]. A subset of 24 patients had additional phosphate measurements at 0-14 days and 15-180 days after remission. In this subgroup, serum phosphate significantly increased from 1.03 ± 0.17 mmol/L prior to remission to 1.22 ± 0.25 mmol/L 15-180 days after remission (p = 0.008). BMI decreased after remission [-1.1 kg/m2, (95%CI -2.09 to -0.07), p=0.037]. Other covariates did not show an equivalent change over time.ConclusionIn this retrospective study, we found that 16% of patients with CS had hypophosphatemia. Moreover, serum phosphate was related to the level of cortisoluria and increased after remission of CS. Potential underlying mechanisms related to urinary phosphate excretion and possibly involving FGF23, BMI and parathyroid hormone levels should be further explored.
Xanthomatous Hypophysitis: A Case Report and Comprehensive Literature Review
Authors: Zhu Jianyu , Wang Zhicheng , Wang Wenze , Fan Jinghua , Zhang Yi , Li Xiaoxu , Liu Jie , Jiang Shenzhong , Deng Kan , Duan Lian , Yao Yong , Zhu Huijuan 
Published: October 2021

PurposeXanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed.MethodsHere, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed.ResultsThe mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% vs. 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68.ConclusionDiagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.
Predictive Modeling of MAFLD Based on Hsp90α and the Therapeutic Application of Teprenone in a Diet-Induced Mouse Model
Authors: Xie Yuan , Chen Lu , Xu Zhipeng , Li Chen , Ni Yangyue , Hou Min , Chen Lin , Chang Hao , Yang Yuxuan , Wang Huiquan , He Rongbo , Chen Rourou , Qian Li , Luo Yan , Zhang Ying , Li Na , Zhu Yuxiao , Ji Minjun , Liu Yu 
Published: October 2021

Background and AimsThe heat shock protein (Hsp) 90α is induced by stress and regulates inflammation through multiple pathways. Elevated serum Hsp90α had been found in nonalcoholic steatohepatitis (NASH). Geranylgeranylacetone (GGA, also called teprenone) is a terpenoid derivative. It was reported to induce Hsp and alleviate insulin resistance. We aimed to evaluate the Hsp90α as a biomarker in predicting metabolic-associated fatty liver disease (MAFLD) and define the therapeutic effects of geranylgeranylacetone for the disease.MethodsA clinical study was conducted to analyze the elements associated with Hsp90α, and a predictive model of MAFLD was developed based on Hsp90α. The histopathological correlation between Hsp90α and MAFLD was investigated through a diet-induced mouse model. Furthermore, GGA was applied to the mouse model.ResultsSerum Hsp90α was increased in patients with MAFLD. A positive linear relationship was found between age, glycosylated hemoglobin (HbA1c), MAFLD, and serum Hsp90α. Meanwhile, a negative linear relationship with body mass index (BMI) was found. A model using Hsp90α, BMI, HbA1c, and ALT was established for predicting MAFLD. The area under the receiver operating characteristic (ROC) curves was 0.94 (95% CI 0.909–0.971, p = 0.000). The sensitivity was 84.1%, and the specificity was 93.1%. In vitro experiments, GGA induced Hsp90α in steatosis cells. In the mice model, Hsp90α decreased in the GGA treatment group. Hepatic steatosis, inflammation, insulin resistance, and glucose intolerance were improved in the GGA-treated group. Serum Hsp90α was positively correlated with steatohepatitis activity according to hepatic histopathology.ConclusionsSerum Hsp90α was elevated in MAFLD, and a positive correlation between serum Hsp90α and the grade of activity of steatohepatitis was observed. The model using BMI, HbA1c, and alanine aminotransferase (ALT) had a good value to predict MAFLD. The findings also revealed the effectiveness of GGA in the treatment of MAFLD.
Newborn Screening for G6PD Deficiency in Xiamen, China: Prevalence, Variant Spectrum, and Genotype-Phenotype Correlations
Authors: Wang Xudong , Xia Zhongmin , He Ying , Zhou Xiaoman , Zhang Haixia , Gao Chunliu , Ge Yunsheng , Cai Xiaofang , Zhou Yulin , Guo Qiwei 
Published: October 2021

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymatic defect. The purpose of this study was to evaluate the profile of G6PD deficiency and investigate the factors associated with the accuracy of newborn screening (NBS) in Xiamen, China.Methods: A total of 99,546 newborns were screened by modified fluorescent spot test at the Women and Children’s Hospital, Xiamen University. High-risk neonates were recalled for diagnosis by either a measurement of G6PD activity or genetic testing for the presence of pathogenic G6PD variants using a quantitative G6PD enzymatic assay or the MeltPro® G6PD assay, respectively.Results: In the first-tier screening, 1,256 newborns were categorized as high risk. Of these, 1,051 were diagnosed with G6PD deficiency, indicating a prevalence of 1.39% in Xiamen, China. Among the 1,013 neonates who underwent genotyping, 851 carried hemizygous, heterozygous, homozygous, or compound heterozygous variants, for a positive predictive value (PPV) of 84.01%. In total, 12 variants and 32 genotypes were identified, and the six most common variants were c.1376G&gt;T, c.1388G&gt;A, c.95A&gt;G, c.1024C&gt;T, c.871G&gt;A, and c.392G&gt;T, which accounted for approximately 94% of the identified alleles. Different variants showed characteristic enzymatic activities, although high phenotypic heterogeneity was observed for each variant. The use of cold-chain transportation significantly improved the PPV of NBS.Conclusions: We determined the profile of G6PD deficiency in Xiamen, including the prevalence, variant spectrum, and genotype-phenotype correlations and confirmed that maintaining a low temperature during sample transport is essential to ensure the high screening accuracy of NBS. Our data provides epidemiological, genotypic, phenotypic, and clinical practice references to standardize future interventions for G6PD deficiency.
Molecular Characterization Analysis of Thalassemia and Hemoglobinopathy in Quanzhou, Southeast China: A Large-Scale Retrospective Study
Authors: Zhuang Jianlong , Zhang Na , Wang Yuanbai , Zhang Hegan , Zheng Yu , Jiang Yuying , Xie Yingjun , Chen Dongmei 
Published: September 2021

Background: There are limited reports available on investigations into the molecular spectrum of thalassemia and hemoglobinopathy in Fujian province, Southeast China. Here, we aim to reveal the spectrum of the thalassemia mutation and hemoglobinopathy in Quanzhou prefecture, Fujian province.Methods: We collected data from a total of 17,407 subjects with the thalassemia trait in Quanzhou prefecture. Gap-PCR, DNA reverse dot blot hybridization, and DNA sequencing were utilized for common and rare thalassemia gene testing.Results: In our study, we identified 7,085 subjects who were carrying thalassemia mutations, representing a detection rate of 40.70% (7,085/17,407). Among them, 13 different α-thalassemia gene mutations were detected, with the most common mutation being –SEA (69.01%), followed by –α3.7 (21.34%) and –α4.2 (3.96%). We also discovered 26 β-thalassemia gene mutations, with the mutations of IVS-II-654 (C &gt; T) (36.28%) and CD41/42(–TCTT) (29.16%) being the most prevalent. Besides, a variety of rare thalassemia variants were identified. Among them, the –FIL, βMalay, βIVS–I–130, and βIVS–II–672 mutations were identified in Fujian province for the first time. Additionally, we detected 78 cases of hemoglobinopathies, of which Hb Owari was the first reported case in Fujian province and Hb Miyashiro was the first case identified in the Chinese population.Conclusion: Our study indicates that there is a diverse range of thalassemia mutations, and it also reveals the mutation spectrum of rare thalassemia and hemoglobinopathies in Quanzhou, Fujian province. It provides valuable data for the prevention and control of thalassemia in Southeast China.
Microdissection of the Bulk Transcriptome at Single-Cell Resolution Reveals Clinical Significance and Myeloid Cells Heterogeneity in Lung Adenocarcinoma
Authors: Wu Hao , Qin Jiale , Zhao Qiang , Lu Lu , Li Chen 
Published: October 2021

BackgroundTumor infiltrating myeloid (TIM) cells constitute a vital element of the tumor microenvironment. The cell-type heterogeneity of TIM has yet to be fully investigated.MethodsWe used a time saving approach to generate a single-cell reference matrix, allowing quantification of cell-type proportions and cell-type-specific gene abundances in bulk RNA-seq data.ResultsTwo distinct clusters, MSC1 and MSC2 (MSC subtype) were newly identified in lung adenocarcinoma (LUAD) patients, both significantly associated with overall survival and immune blockade therapy responses. Twenty myeloid cell types were detected. Thirteen of these had distinct enrichment patterns between MSC1 and MSC2. LAMP3+ dendritic cells, being a mature and transportable subtype of dendritic cell that may migrate to lymph nodes, were noted as associated with non-responsiveness to immunotargeted therapy. High infiltration level of IFIT3+ neutrophils was strongly related to the response to immune-targeted therapy and was seen to activate CD8+ T cells, partly through inflammasome activation. The infiltration levels of TIMP1+ macrophages and S100A8+ neutrophils were both significantly associated with poor prognosis. TIMP1+ macrophages were noted to recruit S100A8+ neutrophils via the CXCL5–CXCR2 axes and promote LUAD progression.ConclusionAltogether, we performed virtual microdissection of the bulk transcriptome at single-cell resolution and provided a promising TIM infiltration landscape that may shed new light on the development of immune therapy.
Association of Myopia With Microvascular Alterations in Patients With Type 2 Diabetes: An Optical Coherence Tomography Angiography Study
Authors: Wen Xin , Li Zijing , Xiao Jianhui , Liu Xuane , Zhang Yichi , Lan Yuqing 
Published: October 2021

Purpose: To determine the association of myopia with peripapillary and macular microvasculature in eyes with type 2 diabetes using optical coherence tomography angiography (OCTA).Methods: Diabetic patients with and without diabetic retinopathy (DR) were recruited and grouped according to myopic status in this cross-sectional study. Axial length, refractive error, and OCTA parameters were measured. OCTA parameters were analyzed with adjustment of confounding factors and further Bonferroni analysis was performed to determine the differences in multiple group comparisons.Results: Compared with the diabetic eyes without myopia, those with myopia had lower rate of DR (21.82 vs. 35.90%, χ2 = 6.190, P = 0.013), longer axial lengths (24.94 ± 0.75 vs. 23.16 ± 0.64, F = 311.055, P &lt; 0.001) and reduced whole vessel density (VD) of optic nerve head (ONH) (45.89 ± 5.76 vs. 49.14 ± 4.33, F = 19.052, P &lt; 0.001), peripapillary VD (48.75 ± 6.56 vs. 50.76 ± 4.51, F = 7.600, P = 0.006), and reduced thickness of the retinal nerve fiber layer (RNFL) (95.50 ± 12.35 vs. 100.67 ± 13.68, F = 5.020, P = 0.026). In eyes without myopia, the superficial vessel density (SVD) (46.58 ± 4.90 vs. 43.01 ± 4.25; 95% CI, 1.80–4.61; P &lt; 0.001), deep vessel density (DVD) (45.64 ± 6.34 vs. 42.15 ± 6.31; 95% CI, 1.07–5.00; P &lt; 0.001), and FD300 area density (50.31 ± 5.74 vs. 44.95 ± 6.96; 95% CI, 2.88–7.27; P &lt; 0.001) were significant reduced in eyes with DR(DR eyes) comparing to those without DR (NoDR eyes). In eyes with myopia, only SVD were significantly reduced in DR eyes comparing to NoDR eyes (41.68 ± 3.34 vs. 45.99 ± 4.17; 95% CI, 1.10–7.22; P = 0.002). In NoDR eyes, both whole VD of ONH and Peripapillary VD demonstrated a significant decrease in eyes with myopia comparing to those without myopia (49.91 ± 4.36 vs. 45.61 ± 6.32; 95% CI, 1.95–6.27; P &lt; 0.001 and 51.36 ± 4.24 vs. 48.52 ± 6.99; 95% CI, 0.56–5.11; P = 0.006, respectively).Conclusions: In diabetic patients, myopic eyes exhibited lower prevalence of DR and thinner thickness of RNFL. The refractive status could possibly impact the retinal microvascular changes from NoDR to DR stage.
Latent Myofascial Trigger Points Injection Reduced the Severity of Persistent, Moderate to Severe Allergic Rhinitis: A Randomized Controlled Trial
Authors: Liu Yu , Yang Yan , Hu Qiya , Badughaish Ahmed , Zhang Hanbing , Qi Feng , Hou Yuedong 
Published: October 2021

Background: Myofascial trigger points (MTrPs) injection has been effectively used for the management of chronic painful diseases. Latent MTrPs can induce autonomic nerve phenomena. In our clinic, we observed that allergic rhinitis (AR) symptoms significantly improved when latent MTrPs injection was performed for migraine.Objective: To compare the efficacy and safety between latent MTrPs injection and sublingual immunotherapy (SLIT) in patients with persistent, moderate to severe AR.Methods: This randomized controlled trial was conducted with 112 patients with AR. Patients were randomized to receive SLIT (n = 56) or latent MTrPs injection. Total nasal symptom score (TNSS, n = 56), nasal symptoms, medication days, and adverse events were evaluated during the 9 months follow-up period after treatment in both groups.Results: Latent MTrPs injection significantly reduced TNSS to a greater level from baseline (from 8.36 ± 1.96 to 4.43 ± 2.18) than SLIT (from 8.66 ± 2.31 to 7.80 ± 2.47) at week 1 (P &lt; 0.001), and sustained the improvement in symptoms throughout to month 9. Latent MTrPs showed statistically significant differences vs. SLIT for the TNSS reduction both at month 2 (6.59 ± 2.37 vs. 2.64 ± 2.38; p &lt; 0.001) and month 3 (4.59 ± 2.77 vs. 2.62 ± 2.43; p &lt;0.001). Latent MTrPs also showed a better improvement in the onset time of efficacy compared with SLIT. Adverse reactions were few and non-serious in both treatment groups.Conclusions: Latent MTrPs injection significantly improved symptoms and decreased symptom-relieving medication use in patients with AR and was well tolerated.Clinical Trials Registration: Chinese Clinical Trial Registry, ChiCTR1900020590. Registered 9 January 2019, http://www.chictr.org.cn/index.aspx.
The Microbial Composition of Lower Genital Tract May Affect the Outcome of in vitro Fertilization-Embryo Transfer
Authors: Wang Ruiying , Zhou Guojun , Wu Lukanxuan , Huang Xin , Li Yujing , Luo Bin , Zhu Huili , Huang Wei 
Published: October 2021

Objective: This work was conducted in order to study the effect of the lower genital tract (vaginal and cervical canal) microbiota on pregnancy outcomes of reproductive-aged women receiving embryo transfer.Study design: A total of 150 reproductive-aged patients who received the first fresh in vitro fertilization-embryo transfer (IVF-ET) were included in the study. Samples from the vagina and cervical site of each patient were collected separately using sterile swabs before ET. Genomic DNA was pyrosequenced for the V3–V4 regions of the 16S ribosomal RNA gene. Further bioinformatics analysis was performed using QIIME and R package. Pregnancy outcomes were followed and analyzed to compare differences in microbial composition.Results: The cervical microbiota had a higher Shannon index than the vaginal microbiota, and the microbial composition was different between the two sites. However, the Sorenson index between the two sites within the same individual was 0.370 (0.309–0.400). A total of 89 patients achieved clinical pregnancy after ET, while 61 failed. The Shannon indices and the microbial community of both vaginal and cervical microbiota between pregnant and non-pregnant groups were not significantly different. The relative abundance of Lactobacillus in the vagina and cervical canal did not differ between the two groups. Linear discriminant analysis, random forest analysis, and receiver-operating characteristic curve analysis showed that Bifidobacterium, Prevotella, and Lactobacillus iners in the vagina, as well as Solanum torvum, Fusobacterium, and Streptococcus in the cervix, may be negatively associated with clinical pregnancy after IVF.Conclusion: The cervical microbiota was more diverse than the vaginal microbiota, but because of anatomical continuity, there was a correlation between the two sites. The microbial composition of the vagina and cervical canal may influence the outcome of IVF-ET, but more samples are needed to verify this conclusion.
A Key Silencing Histone Mark on Chromatin Is Lost When Colorectal Adenocarcinoma Cells Are Depleted of Methionine by Methionine γ-Lyase
Authors: Raboni Samanta , Montalbano Serena , Stransky Stephanie , Garcia Benjamin A. , Buschini Annamaria , Bettati Stefano , Sidoli Simone , Mozzarelli Andrea 
Published: October 2021

Methionine is an essential amino acid used, beyond protein synthesis, for polyamine formation and DNA/RNA/protein methylation. Cancer cells require particularly high methionine supply for their homeostasis. A successful approach for decreasing methionine concentration is based on the systemic delivery of methionine γ-lyase (MGL), with in vitro and in vivo studies demonstrating its efficacy in cancer therapy. However, the mechanisms explaining how cancer cells suffer from the absence of methionine more significantly than non-malignant cells are still unclear. We analyzed the outcome of the human colorectal adenocarcinoma cancer cell line HT29 to the exposure of MGL for up to 72 h by monitoring cell viability, proteome expression, histone post-translational modifications, and presence of spurious transcription. The rationale of this study was to verify whether reduced methionine supply would affect chromatin decondensation by changing the levels of histone methylation and therefore increasing genomic instability. MGL treatment showed a time-dependent cytotoxic effect on HT29 cancer cells, with an IC50 of 30 µg/ml, while Hs27 normal cells were less affected, with an IC50 of &gt;460 µg/ml. Although the levels of total histone methylation were not altered, a loss of the silencing histone mark H3K9me2 was observed, as well as a decrease in H4K20me3. Since H3K9me2/3 decorate repetitive DNA elements, we proved by qRT-PCR that MGL treatment leads to an increased expression of major satellite units. Our data indicate that selected histone methylation marks may play major roles in the mechanism of methionine starvation in cancer cells, proving that MGL treatment directly impacts chromatin homeostasis.
Association of Circulating T Follicular Helper Cells With Idiopathic Optic Neuritis and Neuromyelitis Optica Spectrum Disorders
Authors: Wu Qian , Yang Binbin , Wang Jiawei 
Published: October 2021

Background: T follicular helper cells (Tfh cells) play an important role in activating B lymphocytes and may associate with idiopathic Optic Neuritis (ON) and Neuromyelitis Optica Spectrum Disorders (NMOSD).Objective: This study aimed to examine the potential role of Tfh cells in pathogenesis of idiopathic ON and NMOSD.Methods: Circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+ cells in 46 idiopathic ON and 68 NMOSD patients as well as 28 healthy controls were examined by flow cytometry before treatment. Serum AQP4 antibody, Expended Disability Status Scale (EDSS) and Visual Outcome Scale (VOS) were detected before and after treatment.Results: The percentages of circulating CD4+CXCR5+ and CD4+CXCR5+PD-1+Tfh cells in CD4+ cells (%) were significantly increased in idiopathic ON and NMOSD compared with those of healthy controls (p &lt; 0.01). No significant difference of Tfh cells in blood and cerebral spinal fluid (CSF) was found between ON and NMOSD patients. The percentages of CSF, CD4+, CXCR5+, and CD4+CXCR5+PD-1+ cells in CD4+ cells (%) were positively correlated with those of the blood (r = 0.5781, r = 0.6079, p = 0.0076, and p = 0.0045, respectively). EDSS scores of NMOSD group were higher than those of ON group and the time course of NMOSD patients was longer than that of ON patients (p &lt; 0.01). After methylprednisolone treatment, both EDSS and VOS scores were significantly decreased at discharge compared with before treatment (p &lt; 0.01). There was no significant correlation among Tfh cell percentages in CD4+ cells, CSF leukocytes, CSF protein, annual recurrence rate, EDSS and VOS scores between two groups (p &gt; 0.05).Conclusion: The Circulating T follicular helper cells were increased in both idiopathic ON and NMOSD.