bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between 25(OH)Vitamin D, HbA1c and Albuminuria in Diabetes Mellitus: Data From a Population-Based Study (VIDAMAZON)
Authors: Felício João Soares , de Rider Britto Hana Andrade , Cortez Pedro Celeira , de Souza Resende Fabrício , de Lemos Manuela Nascimento , de Moraes Lorena Vilhena , de Aquino Vitória Teixeira , de Souza Parente Fernanda , de Queiroz Natércia Neves Marques , Abrahão Neto João Felício , de Alcântara Angélica Leite , da Silva Wanderson Maia , de Souza Neto Norberto Jorge Kzan , Freire Piani Pedro Paulo , de Souza Ícaro José Araújo , Silva Lilian de Souza D’Albuquerque , de Oliveira Maria Clara Neres Iunes , Said Nivin Mazen , Nascimento de Lemos Gabriela , de Melo Franciane Trindade Cunha , Gomes Daniela Lopes , Contente Braga de Souza Ana Carolina , de Sá Oliveira dos Reis Melissa , Leal Valéria Suênya Galvão , Lobato Isabel Jane Campos , Felício Karem Miléo 
Published: October 2021

BackgroundThe effect of glycemic control on diabetic kidney disease (DKD) is well known. Recent evidence has suggested that Vitamin D (VD) may have a nephroprotective effect in diabetes, but the relationship between VD, glycemic control, and albuminuria has yet to be clarified.ObjectiveEvaluate the relationship between 25-hydroxy-vitamin D [25(OH)D], HbA1c, and albuminuria in Diabetes Mellitus (DM).Patients and MethodsCross-sectional study with 1576 individuals with DM who had 25(OH)D, HbA1c, and albuminuria levels measured. Patients with abnormal creatinine levels were excluded, in order to avoid interference on VD levels by impaired kidney function.ResultsPatients with HbA1c ≥7% had lower 25(OH)D when compared to patients with HbA1c &lt;7% (29.7 ± 10.2 vs 28.1 ± 9.9 ng/ml, p = 0.003) and 25(OH)D levels seems to predict 1.5% of HbA1c behavior. The 25(OH)D concentrations in patients with normoalbuminuria were higher than the levels observed in those with micro or macroalbuminuria (29.8 ± 9.0 vs 26.8 ± 8.6 and 25.1 ± 7.6, respectively, p = 0.001), patients who had 25(OH)D &lt;20 ng/ml and 25(OH)D &lt;30 ng/ml were at a higher risk of presenting albuminuria [OR = 2.8 (95% CI = 1.6 – 4.9), p&lt;0.001, and OR = 2.1 (95% CI = 1.3 - 4.6), p&lt;0.001, respectively]. In our regression model, albuminuria was influenced by HbA1c (r² = 0.076, p&lt;0.00001) and 25(OH)D (r² = 0.018, p = 0.002) independently.ConclusionOur study found an association between vitamin D levels, HbA1c and DKD. Additionally, our data suggest that the association between urinary albumin excretion and vitamin D levels is independent of glycemic control in patients with diabetes. Even though our patients presented normal creatinine levels, it is necessary further prospective studies to confirm if this association precedes or not the loss of renal function.
Bariatric Surgery Induces a Differential Effect on Plasma Aldosterone in Comparison to Dietary Advice Alone
Authors: Berney Maxime , Vakilzadeh Nima , Maillard Marc , Faouzi Mohamed , Grouzmann Eric , Bonny Olivier , Favre Lucie , Wuerzner Grégoire 
Published: October 2021

Background and ObjectivesThe pathophysiological mechanisms linking weight loss to blood pressure (BP) reduction are not completely understood. The objective of this study was to compare the effect of weight loss after Roux-en-Y gastric bypass (RYGB) on BP, renin-angiotensin-aldosterone system (RAAS), and urinary electrolytes excretion to those of dietary advice.MethodsThis was a case-control prospective study including obese patients referred for RYGB (cases) and obese receiving diet advice only (controls). Ambulatory BP, plasma renin activity (PRA), plasma aldosterone concentration (PAC), and urinary electrolytes were measured before (M0) and after intervention (M3: 3 months and M12: 12 months).ResultsTwenty-five patients were included in the RYGB group and twelve patients in the control group. After 12 months, weight loss (-42 ± 11.5 vs -12.3 ± 6.3 kg in the control group, p=0.001) and decrease in PAC were more pronounced in the RYGB group (-34 ± 76 vs +14 ± 45 pg/ml in the control group, p=0.002). There was no difference in PRA between both groups (-0.08 ± 1.68 vs 0.01 ± 0.37 ng/ml/h, p=0.31). Sodium excretion was more marked in the RYGB group after 3 months only (-89 ± 14.9 vs -9.9 ± 27.9 mmol/day, p=0.009). The decrease in SBP was similar between both groups (-6.9 ± 9.9 vs -7.1 ± 11.9 mmHg in the control group, p=0.96).ConclusionsBariatric-induced weight loss induces a progressive decrease in PAC independently of PRA and sodium excretion. Whether this decrease in PAC affects target organ damage in the long term remains to be determined.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02218112.
Case Report: A Case of Epileptic Disorder Associated With a Novel CNTN2 Frameshift Variant in Homozygosity due to Maternal Uniparental Disomy
Authors: Chen Wenjie , Chen Fei , Shen Yiping , Yang Zhixian , Qin Jiong 
Published: October 2021

Background: Contactin 2, encoded by CNTN2 on chromosome 1q32.1, is a neural-specific glycoprotein and plays important roles in neurodevelopment. A deleterious homozygous variant in the CNTN2 gene was previously reported to cause autosomal recessive cortical myoclonic tremor and epilepsy. Since then, there has been no further report confirming the association of CNTN2 and epilepsy. Here, we reported one new case, who presented with epilepsy, carrying a novel homozygous frameshift variant in CNTN2. The clinical and genetic features of the patient were reviewed.Case presentation: The male patient presented with preschool age-of-onset neurodevelopmental impairment and focal seizures of temporal origin, and responded to valproate. A trio-whole exome sequencing revealed a novel homozygous frameshift variant in CNTN2 (c.2873_c.2874delCT, p.Thr958Thrfs). The patient’s mother was a heterozygous carrier while his father was wild-type; they were both unaffected and non-consanguineous. Further study revealed that maternal uniparental disomy (1q32.1) unmasked the heterozygous variant of CNTN2 in the proband.Conclusions: This case enhanced the gene–disease relationship between CNTN2 and epilepsy, which will help to further understand this emerging disorder.
CD19 CAR-T Cells With Membrane-Bound IL-15 for B-Cell Acute Lymphoblastic Leukemia After Failure of CD19 and CD22 CAR-T Cells: Case Report
Authors: Sun Yao , Su Yongfeng , Wang Yizhi , Liu Na , Li Yuhang , Chen Jianlin , Qiao Zhuoqing , Niu Jingwen , Hu Jiangwei , Zhang Bin , Ning Hongmei , Hu Liangding 
Published: October 2021

ObjectivesAt present, reinfusions of chimeric antigen receptor (CAR)-T cell have exhibited limited efficacy, while their efficacy on extramedullary relapse remains to be further elucidated in B-cell acute lymphoblastic leukemia (B-ALL). Although combination with IL-15 demonstrated the potential to enhance antitumor activity of CAR-T, the efficacy of this approach remains to be validated clinically.MethodsWe reported a patient with B-ALL with extramedullary relapse after allogeneic stem cell transplantation and who was resistant to chemotherapy and radiotherapy. In total, he received four treatments with CAR-T cells repeatedly under the status of disease progression.ResultsFirst, the patient received autologous murine CAR19-CD28-CD3ζ-T cells and achieved full resolution of extramedullary leukemia lasting 8 months. After systemic disease relapse, he received autologous humanized CAR22-41BB-CD3ζ-tEGFR-T cells and achieved complete remission (CR) with incomplete blood count recovery (CRi) with minimal residual disease (MRD) negativity in the bone marrow and shrinkage of extramedullary leukemia. Over 2 months later, he experienced a relapse of the systemic disease and he received autologous murine CAR19-41BB-CD3ζ-mIL15-T cells and achieved CRiMRD- lasting 5 months with the strongest expansion and persistence of CAR. Finally, on relapse of CD19− medullary disease, he received allogeneic humanized CAR22-41BB-CD3ζ-tEGFR-T cells but only achieved a transient decrease in the number of blasts. No CAR-T-cell-related encephalopathy syndrome was observed, and all side effects were manageable.ConclusionOur report hints the feasibility and safety of CD19 CAR-T cell expressing membrane-bound IL-15 for patient with B-ALL even if relapsed after multiple CAR-T-cell therapies.
Sensory Percepts Elicited by Chronic Macro-Sieve Electrode Stimulation of the Rat Sciatic Nerve
Authors: Chandra Nikhil S. , McCarron Weston M. , Yan Ying , Ruiz Luis C. , Sallinger Eric G. , Birenbaum Nathan K. , Burton Harold , Green Leonard , Moran Daniel W. , Ray Wilson Z. , MacEwan Matthew R. 
Published: October 2021

Objective: Intuitive control of conventional prostheses is hampered by their inability to provide the real-time tactile and proprioceptive feedback of natural sensory pathways. The macro-sieve electrode (MSE) is a candidate interface to amputees’ truncated peripheral nerves for introducing sensory feedback from external sensors to facilitate prosthetic control. Its unique geometry enables selective control of the complete nerve cross-section by current steering. Unlike previously studied interfaces that target intact nerve, the MSE’s implantation requires transection and subsequent regeneration of the target nerve. Therefore, a key determinant of the MSE’s suitability for this task is whether it can elicit sensory percepts at low current levels in the face of altered morphology and caliber distribution inherent to axon regeneration. The present in vivo study describes a combined rat sciatic nerve and behavioral model developed to answer this question.Approach: Rats learned a go/no-go detection task using auditory stimuli and then underwent surgery to implant the MSE in the sciatic nerve. After healing, they were trained with monopolar electrical stimuli with one multi-channel and eight single-channel stimulus configurations. Psychometric curves derived by the method of constant stimuli (MCS) were used to calculate 50% detection thresholds and associated psychometric slopes. Thresholds and slopes were calculated at two time points 3 weeks apart.Main Results: For the multi-channel stimulus configuration, the average current required for stimulus detection was 19.37 μA (3.87 nC) per channel. Single-channel thresholds for leads located near the nerve’s center were, on average, half those of leads located near the periphery (54.92 μA vs. 110.71 μA, or 10.98 nC vs. 22.14 nC). Longitudinally, 3 of 5 leads’ thresholds decreased or remained stable over the 3-week span. The remaining two leads’ thresholds increased by 70–74%, possibly due to scarring or device failure.Significance: This work represents an important first step in establishing the MSE’s viability as a sensory feedback interface. It further lays the groundwork for future experiments that will extend this model to the study of other devices, stimulus parameters, and task paradigms.
Overexpression of Long Non-Coding RNA Linc01315 Predicts Poor Prognosis in Breast Cancer
Authors: Xue Jingyan , Huang Sheng , Chen Jiaying , Chen Yi-zuo , Shao Zhi-min , Wu Jiong , Chi Yayun 
Published: October 2021

BackgroundLncRNAs have been shown to play critical roles in regulating tumorigenesis and tumor progression. Using LncRNAs to predict prognosis and therapeutic response to cancer treatment has been caused for concern, but the predictive value of lncRNAs remains to be explored and underlying mechanisms have not been completely understood.MethodsThe Linc01315 expression level was detected in 282 breast cancer tissues by using quantitative RT-PCR. The association between Linc01315 expression level and clinicopathological features of these breast cancer patients was further analyzed. Multiple regression analysis was used to evaluate Linc01315 predictive value of patients’ prognosis.ResultsOur study revealed that Linc01315 expression level was significantly correlated with vessel invasion (P = 0.028) and tumor subtype (P = 0.039). The Kaplan–Meier survival curves demonstrated that patients with lower Linc01315 expression level had significantly longer disease free survival (DFS) (P = 0.002) and overall survival (OS) (P=0.019). Multiple regression analysis showed that Linc01315 level could be an independent predictive factor for DFS (hazards ratio = 0.613, 95% confidence interval = 0.375-1.003; P = 0.049) and OS (hazards ratio = 0.439, 95% confidence interval = 0.228-0.845; P = 0.014). Further analysis showed that low Linc01315 level patients with endocrine therapy could benefit patients DFS (P=0.037) and OS (P=0.025).ConclusionOur results demonstrate that Linc01315 expression level is significantly correlated with breast cancer patients’ prognosis. Linc01315 may represent an independent prognostic marker and therapeutic target in breast cancer.
Evaluation of Diagnostic Potential of Epigenetically Deregulated MiRNAs in Epithelial Ovarian Cancer
Authors: Kumar Vivek , Gupta Sameer , Chaurasia Amrita , Sachan Manisha 
Published: October 2021

BackgroundEpithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies among women worldwide. Early diagnosis of EOC could help in ovarian cancer management. MicroRNAs, a class of small non-coding RNA molecules, are known to be involved in post-transcriptional regulation of ~60% of human genes. Aberrantly expressed miRNAs associated with disease progression are confined in lipid or lipoprotein and secreted as extracellular miRNA in body fluid such as plasma, serum, and urine. MiRNAs are stably present in the circulation and recently have gained an importance to serve as a minimally invasive biomarker for early detection of epithelial ovarian cancer.MethodsGenome-wide methylation pattern of six EOC and two normal ovarian tissue samples revealed differential methylation regions of miRNA gene promoter through MeDIP-NGS sequencing. Based on log2FC and p-value, three hypomethylated miRNAs (miR-205, miR-200c, and miR-141) known to have a potential role in ovarian cancer progression were selected for expression analysis through qRT-PCR. The expression of selected miRNAs was analyzed in 115 tissue (85 EOC, 30 normal) and 65 matched serum (51 EOC and 14 normal) samples.ResultsAll three miRNAs (miR-205, miR-200c, and miR-141) showed significantly higher expression in both tissue and serum cohorts when compared with normal controls (p &lt; 0.0001). The receiver operating characteristic curve analysis of miR-205, miR-200c, and miR-141 has area under the curve (AUC) values of 87.6 (p &lt; 0.0001), 78.2 (p &lt; 0.0001), and 86.0 (p &lt; 0.0001), respectively; in advance-stage serum samples, however, ROC has AUC values of 88.1 (p &lt; 0.0001), 78.9 (p &lt; 0.0001), and 86.7 (p &lt; 0.0001), respectively, in early-stage serum samples. The combined diagnostic potential of the three miRNAs in advance-stage serum samples and early-stage serum samples has AUC values of 95.9 (95% CI: 0.925–1.012; sensitivity = 96.6% and specificity = 80.0%) and 98.1 (95% CI: 0.941–1.021; sensitivity = 90.5% and specificity = 100%), respectively.ConclusionOur data correlate the epigenetic deregulation of the miRNA genes with their expression. In addition, the miRNA panel (miR-205 + miR-200c + miR-141) has a much higher AUC, sensitivity, and specificity to predict EOC at an early stage in both tissue and serum samples.
Reduced Intensity Conditioning Followed by Allogeneic Hematopoietic Stem Cell Transplantation Is a Good Choice for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Meta-Analysis of Randomized Controlled Trials
Authors: Song Yanzhi , Yin Zhichao , Ding Jie , Wu Tong 
Published: October 2021

BackgroundReduced intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been reported to have the same overall survival (OS) as myeloablative conditioning (MAC) for patients with acute myeloid leukemia (AML) in complete remission (CR) and myelodysplastic syndrome (MDS). However, results from different studies are conflicting. Therefore, we conducted a systematic review and meta-analysis guided by PRISMA 2009 to confirm the efficacy and safety of RIC vs. MAC for AML in CR and MDS.MethodsWe search PubMed, Web of Science, Embase, Cochrane central, clinical trial registries and related websites, major conference proceedings, and field-related journals from January 1, 1980, to July 1, 2020, for studies comparing RIC with MAC before the first allo-HSCT in patients with AML in CR or MDS. Only randomized controlled trials (RCTs) were included. OS was the primary endpoint and generic inverse variance method was used to combine hazard ratio (HR) and 95% CI.ResultsWe retrieved 7,770 records. Six RCTs with 1,413 participants (711 in RIC, 702 in MAC) were included. RIC had the same OS (HR = 0.95, 95% CI 0.64–1.4, p = 0.80) and cumulative incidence of relapse as MAC (HR = 1.18, 95% CI 0.88–1.59, p = 0.28). Furthermore, RIC significantly reduced non-relapse mortality more than total body irradiation/busulfan-based MAC (HR = 0.53, 95% CI 0.36–0.80, p = 0.002) and had similar long-term OS and graft failure as MAC.ConclusionRIC conditioning regimens are recommended as an adequate option of preparative treatment before allo-HSCT for patients with AML in CR or MDS.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185436.
Investigation of Predictors to Achieve Acceptable Lung Dose in T-Shaped Upper and Middle Esophageal Cancer With IMRT and VMAT
Authors: Shao Yan , Chen Hua , Wang Hao , Duan Yanhua , Feng Aihui , Huang Ying , Gu Hengle , Kong Qing , Xu Zhiyong 
Published: October 2021

PurposeThe purpose of this study is to investigate whether there are predictors and cutoff points that can predict the acceptable lung dose using intensity-modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) in radiotherapy for upper ang middle esophageal cancer.Material and MethodsEighty-two patients with T-shaped upper-middle esophageal cancer (UMEC) were enrolled in this retrospective study. Jaw-tracking IMRT plan (JT-IMRT), full-arc VMAT plan (F-VMAT), and pactial-arc VMAT plan (P-VMAT) were generated for each patient. Dosimetric parameters such as MLD and V20 of total lung were compared among the three plannings. Ten factors such as PCTVinferior length and PCTVinferior length/total lung length were calculated to find the predictors and cutoff points of the predictors. All patients were divided into two groups according to the cutoff points, and the dosimetric differences between the two groups of the three plans were compared. ANOVA, receiver operating characteristic (ROC) analysis, and Mann–Whitney U-test were performed for comparisons between datasets. A p &lt;0.05 was considered statistically significant.ResultThe quality of the targets of the three plannings was comparable. The total lung dose in P-VMAT was significantly lower than that in JT IMRT and F-VMAT. Monitor unit (MU) of F-VMAT and P-VMAT was significantly lower than that of JT IMRT. ROC analysis showed that among JT IMRT, F-VMAT, and P-VMAT, PCTVi-L, and PCTVi-L/TLL had diagnostic power to predict the suitability of RT plans according to lung dose constraints of our department. For JT IMRT, the cutoff points of PCTVi-L and PCTVi-L/TLL were 16.6 and 0.59. For F-VMAT, the cutoff points of PCTVi-L and PCTVi-L/TLL were 16.75 and 0.62. For P-VMAT, the cutoff points of PCTVi-L and PCTVi-L/TLL were 15.15 and 0.59. After Mann–Whitney U-test analysis, it was found that among the three plannings, the group with lower PCTVi-L and PCTVi-L/TLL could significantly reduce the dose of total lung and heart (p &lt;0.05).ConclusionPCTVi-L &lt;16.6 and PCTVi-L/TLL &lt;0.59 for JT IMRT, PCTVi-L &lt;16.75 and PCTVi-L/TLL &lt;0.62 for F-VMAT and PCTVi-L &lt;15.15, and PCTVi-L/TLL &lt;0.59 for P-VMAT can predict whether patients with T-shaped UMEC can meet the lung dose limits of our department.
Cancer Cell-Derived Exosomes Promote HCC Tumorigenesis Through Hedgehog Pathway
Authors: Li Li , Zhao Jing , Zhang Quanbao , Tao Yifeng , Shen Conghuan , Li Ruidong , Ma Zhengyu , Li Jianhua , Wang Zhengxin 
Published: October 2021

PurposeHepatocellular carcinoma (HCC) accounts for more than 80% of primary liver cancers and is one of the leading causes of cancer-related death in many countries. Cancer cell-derived exosomes are shown to mediate communications between cancer cells and the microenvironment, promoting tumorigenesis. Hedgehog signaling pathway plays important roles in cancer development of HCC.MethodsExosomes were isolated from culture medium of HCC cell lines PLC/PRF/5 and MHCC-97H and were found to promote cancer cell growth measured with cell proliferation and colony formation assay. HCC cells cultured with cancer cell-derived exosome had increased cancer stem cell (CSC) population demonstrated by increased cell sphere formation CSC marker expressions. Hedgehog protein Shh was found to be highly expressed in these two HCC cell lines and preferably carried by exosomes. When Shh was knocked down with shRNA, the resulting exosomes had a reduced effect on promoting cancer cell growth or CSC population increase compared to normal cell-derived exosomes.ResultsThe ability of PLC/PRF/5 cells to form tumor in a xenograft model was increased by the addition of the exosomes from control cancer cells but not the exosomes from Shh knocked down cancer cells. Finally, the higher plasma Exo-Shh levels were associated with later tumor stages, higher histological grades, multiple tumors, and higher recurrence rates.ConclusionThis study demonstrated that HCC cells secreted Shh via exosome and promote tumorigenesis through the activated Hedgehog pathway.
Analysis of Global and Local DNA Methylation Patterns in Blood Samples of Patients With Autism Spectrum Disorder
Authors: García-Ortiz María Victoria , Torre-Aguilar María José de la , Morales-Ruiz Teresa , Gómez-Fernández Antonio , Flores-Rojas Katherine , Gil-Campos Mercedes , Martin-Borreguero Pilar , Ariza Rafael R. , Roldán-Arjona Teresa , Perez-Navero Juan Luis 
Published: October 2021

The goal of this investigation was to determine whether there are alterations in DNA methylation patterns in children with autism spectrum disorder (ASD).Material and Methods: Controlled prospective observational case-control study. Within the ASD group, children were sub-classified based on the presence (AMR subgroup) or absence (ANMR subgroup) of neurodevelopmental regression during the first 2 years of life. We analyzed the global levels of DNA methylation, reflected in LINE-1, and the local DNA methylation pattern in two candidate genes, Neural Cell Adhesion Molecule (NCAM1) and Nerve Growth Factor (NGF) that, according to our previous studies, might be associated to an increased risk for ASD. For this purpose, we utilized blood samples from pediatric patients with ASD (n = 53) and their corresponding controls (n = 45).Results: We observed a slight decrease in methylation levels of LINE-1 in the ASD group, compared to the control group. One of the CpG in LINE-1 (GenBank accession no.X58075, nucleotide position 329) was the main responsible for such reduction, highly significant in the ASD subgroup of children with AMR (p &lt; 0.05). Furthermore, we detected higher NCAM1 methylation levels in ASD children, compared to healthy children (p &lt; 0.001). The data, moreover, showed higher NGF methylation levels in the AMR subgroup, compared to the control group and the ANMR subgroup. These results are consistent with our prior study, in which lower plasma levels of NCAM1 and higher levels of NGF were found in the ANMR subgroup, compared to the subgroup that comprised neurotypically developing children.Conclusions: We have provided new clues about the epigenetic changes that occur in ASD, and suggest two potential epigenetic biomarkers that would facilitate the diagnosis of the disorder. We similarly present with evidence of a clear differentiation in DNA methylation between the ASD subgroups, with or without mental regression.