bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Aegle Marmelos Fruit Pulp Powder on Chronic Subclinical Inflammatory Status (Phase 3 clinical trial) of Type 2 Diabetic Patients
Authors: Aziz Murshida , Debnath Rupali , Ayub Tohfa E , Islam Fahmida , Aktar Farjana , Aman Safwanul 
Published: May 2021

Background: The plant is reported to have multiple therapeutic properties such as chronic subclinical inflammation.
Objective: In this present study Aegle marmelos was investigated for its anti-inflammatory effects on human T2DM subjects.
Methodology: The present study was conducted at Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka, Bangladesh from July 2010 to June 2011 to explore the effect of Aegle marmelos unripe fruit pulp on chronic subclinical inflammatory status in T2DM patients as evident by hsCRP. It was an un-blinded clinical trial conducted under a cross-over design. The experiment was conducted under a crossover design and the effects were analyzed during the 0-21 as well as 28-49 days with 7 days wash out period. The data were then pooled and the baseline versus endpoint values was also compared.
Result: The mean blood hsCRP values did not significantly differ between the intervention and control groups at any time points. No significant difference between the baseline and end point values regarding blood hsCRP. The effect on blood hsCRP was not significant in any of the analysis.
Conclusion: This study reveals no changes in chronic subclinical inflammatory status of Aegle marmelos fruit pulp in T2DM patients.
Journal of Current and Advance Medical Research, January 2021;8(1):17-20
Biomechanical Effects of a Cross Connector in Sacral Fractures – A Finite Element Analysis
Authors: Gierig Meike , Liu Fangrui , Weiser Lukas , Lehmann Wolfgang , Wriggers Peter , Marino Michele , Saul Dominik 
Published: May 2021

Background:Spinopelvic fractures and approaches of operative stabilization have been a source of controversial discussion. Biomechanical data support the benefit of a spinopelvic stabilization and minimally invasive procedures help to reduce the dissatisfying complication rate. The role of a cross connector within spinopelvic devices remains inconclusive. We aimed to analyze the effect of a cross connector in a finite element model (FE model).Study Design:A FE model of the L1-L5 spine segment with pelvis and a spinopelvic stabilization was reconstructed from patient-specific CT images. The biomechanical relevance of a cross connector in a Denis zone I (AO: 61-B2) sacrum fracture was assessed in the FE model by applying bending and twisting forces with and without a cross connector. Biomechanical outcomes from the numerical model were investigated also considering uncertainties in material properties and levels of osseointegration.Results:The designed FE model showed comparable values in range-of-motion (ROM) and stresses with reference to the literature. The superiority of the spinopelvic stabilization (L5/Os ilium) ± cross connector compared to a non-operative procedure was confirmed in all analyzed loading conditions by reduced ROM and principal stresses in the disk L5/S1, vertebral body L5 and the fracture area. By considering the combination of all loading cases, the presence of a cross connector reduced the maximum stresses in the fracture area of around 10%. This difference has been statistically validated (p&lt; 0.0001).Conclusion:The implementation of a spinopelvic stabilization (L5/Os ilium) in sacrum fractures sustained the fracture and led to enhanced biomechanical properties compared to a non-reductive procedure. While the additional cross connector did not alter the resulting ROM in L4/L5 or L5/sacrum, the reduction of the maximum stresses in the fracture area was significant.
The Controlled Synthesis of Birnessite Nanoflowers via H2O2 Reducing KMnO4 For Efficient Adsorption and Photooxidation Activity
Authors: Li Yang , Jiang Guanjie , Ouyang Nanqi , Qin Zhangjie , Lan Shuai , Zhang Qin 
Published: May 2021

Birnessite nanoflowers composed of layers have been proven to be the strongest adsorbent and oxidant in the surface environment. However, the current synthesis methods of birnessite nanoflowers are suffering from long reaction time and high reaction temperature. Based on these, this paper explores a new method for the rapid and controlled synthesis of layered manganese oxides. The method relies on the molar ratios of KMnO4 and H2O2 redox reacting species to drive the production of birnessite nanoflowers under acidic conditions. The molar ratios of KMnO4 and H2O2 are the key to the crystal structure of the as-prepared. It was found that when the molar ratios of KMnO4 and H2O2 is from 1:1.25 to 1:1.90, the sample is birnessite nanoflowers, and when the ratio is increased to 1:2.0, the sample is a mixture of birnessite nanoflowers and feitknechtite nanoplates. Among the as-prepared samples, BF-1.85 (molar ratios of KMnO4 and H2O2 is 1:1.85) shows the highest capacity for Pb2+ adsorption (2,955 mmol/kg) and greatest degradation efficiency of phenol and TOC. The method proposed herein is economical and controllable, and it yields products with high efficiency for the elimination of inorganic and organic pollutants.
Circ_0068087 Silencing Ameliorates Oxidized Low-Density Lipoprotein-Induced Dysfunction in Vascular Endothelial Cells Depending on miR-186-5p-Mediated Regulation of Roundabout Guidance Receptor 1
Authors: Li Shuanghong , Huang Tao , Qin Limin , Yin Luchang 
Published: May 2021

Background: Circular RNAs (circRNAs) are endogenous non-coding RNAs involved in the progression of atherosclerosis (AS). We investigated the role of circ_0068087 in AS progression and its associated mechanism.Methods: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze the viability, apoptosis, and inflammatory response of HUVECs, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the Western blot assay were performed to measure the expression of RNA and protein. Cell oxidative stress was analyzed using commercial kits. The dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the interaction between microRNA-186-5p (miR-186-5p) and circ_0068087 or roundabout guidance receptor 1 (ROBO1).Results: Oxidized low-density lipoprotein (ox-LDL) exposure upregulated the circ_0068087 level in HUVECs. ox-LDL-induced dysfunction in HUVECs was largely attenuated by the silence of circ_0068087. Circ_0068087 negatively regulated the miR-186-5p level by interacting with it in HUVECs. Circ_0068087 knockdown restrained ox-LDL-induced injury in HUVECs partly by upregulating miR-186-5p. ROBO1 was a downstream target of miR-186-5p in HUVECs. Circ_0068087 positively regulated ROBO1 expression by sponging miR-186-5p in HUVECs. MiR-186-5p overexpression exerted a protective role in ox-LDL-induced HUVECs partly by downregulating ROBO1.Conclusion: Circ_0068087 interference alleviated ox-LDL-induced dysfunction in HUVECs partly by reducing ROBO1 expression via upregulating miR-186-5p.
The Leukocyte Subtype Counts and Ratios Can Effectively Predict the Risk of Arterial Stiffness Assessed by Cardio-Ankle Vascular Index: A Retrospective Study
Authors: Wang Yaoling , Wang Ruiyun , Bai Lijuan , Liu Yun , Liu Lihua , He Linfeng , Qi Benling 
Published: May 2021

Background: Arterial stiffness was the pathological basis and risk factor of cardiovascular diseases, with chronic inflammation as the core characteristic. We aimed to analyze the association between the arterial stiffness measured by cardio-ankle vascular index (CAVI) and indicators reflecting the inflammation degree, such as count of leukocyte subtypes, platelet, and monocyte-to-lymphocyte ratio (MLR), etc.Methods: The data of inpatients from November 2018 to November 2019 and from December 2019 to September 2020 were continuously collected as the training set (1,089 cases) and the validation set (700 cases), respectively. A retrospective analysis of gender subgroups was performed in the training set. The association between inflammatory indicators and CAVI or arterial stiffness by simple linear regression, multiple linear regression, and logistic regression was analyzed. The effectiveness of the inflammation indicators and the CAVI decision models to identify arterial stiffness by receiver operating curve (ROC) in the training and validation set was evaluated.Results: The effect weights of MLR affecting the CAVI were 12.87% in men. MLR was the highest risk factor for arterial stiffness, with the odds ratio (95% confidence interval) of 8.95 (5.04–184.79) in men after adjusting the covariates. A cutpoint MLR of 0.19 had 70% accuracy for identifying arterial stiffness in all participants. The areas under the ROC curve of the CAVI decision models for arterial stiffness were &gt;0.80 in the training set and validation set.Conclusions: The MLR might be a high-risk factor for arterial stiffness and could be considered as a potential indicator to predict arterial stiffness.
Randomized Sham-Controlled Pilot Study of Neurocardiac Function in Patients With Acute Ischaemic Stroke Undergoing Heart Rate Variability Biofeedback
Authors: Siepmann Timo , Ohle Paulin , Sedghi Annahita , Simon Erik , Arndt Martin , Pallesen Lars-Peder , Ritschel Gerhard , Barlinn Jessica , Reichmann Heinz , Puetz Volker , Barlinn Kristian 
Published: May 2021

Background: Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS).Methods: We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV via standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed via survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months.Results: We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, p = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, p = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, p = 0.029], which was not seen after sham biofeedback (SDNN: p = 0.63, RMSSD: p = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function (p = ns).Conclusions: Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03865225.
Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors
Authors: Tso Winnie Wan Yee , Hui Edward Sai Kam , Lee Tatia Mei Chun , Liu Anthony Pak Yin , Ip Patrick , Vardhanabhuti Vince , Cheng Kevin King Fai , Fong Daniel Yee Tak , Chang Dorita Hue Fung , Ho Frederick Ka Wing , Yip Ka Man , Ku Dennis Tak Loi , Cheuk Daniel Ka Leung , Luk Chung Wing , Shing Ming Kong , Leung Lok Kan , Khong Pek Lan , Chan Godfrey Chi-Fung 
Published: May 2021

BackgroundChildhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors.MethodsDKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof.ResultsThe mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 – 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P &lt; 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions.ConclusionOur study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.
NOTCH1 Activation Negatively Impacts on Chronic Lymphocytic Leukemia Outcome and Is Not Correlated to the NOTCH1 and IGHV Mutational Status
Authors: Baldoni Stefano , Del Papa Beatrice , De Falco Filomena , Dorillo Erica , Sorrentino Carlo , Rompietti Chiara , Adamo Francesco Maria , Nogarotto Manuel , Cecchini Debora , Mondani Elena , Silva Barcelos Estevao Carlos , Moretti Lorenzo , Mameli Maria Grazia , Fabi Bianca , Sorcini Daniele , Stella Arianna , Giancola Raffaella , Guardalupi Francesco , Ulbar Francesca , Plebani Sara , Guarente Valerio , Rosati Emanuela , Di Nicola Marta , Marchioni Michele , Di Ianni Mauro , Sportoletti Paolo 
Published: May 2021

NOTCH1 mutations and deregulated signal have been commonly found in chronic lymphocytic leukemia (CLL) patients. Whereas the impact of NOTCH1 mutations on clinical course of CLL has been widely studied, the prognostic role of NOTCH1 activation in CLL remains to be defined. Here, we analyzed the activation of NOTCH1/NOTCH2 (ICN1/ICN2) and the expression of JAGGED1 (JAG1) in 163 CLL patients and evaluated their impact on TTFT (Time To First Treatment) and OS (Overall Survival). NOTCH1 activation (ICN1+) was found in 120/163 (73.6%) patients. Among them, 63 (52.5%) were NOTCH1 mutated (ICN1+/mutated) and 57 (47.5%) were NOTCH1 wild type (ICN1+/WT). ICN1+ patients had a significant reduction of TTFT compared to ICN1-negative (ICN1−). In the absence of NOTCH1 mutations, we found that the ICN1+/WT group had a significantly reduced TTFT compared to ICN1− patients. The analysis of IGHV mutational status showed that the distribution of the mutated/unmutated IGHV pattern was similar in ICN1+/WT and ICN1− patients. Additionally, TTFT was significantly reduced in ICN1+/ICN2+ and ICN1+/JAG1+ patients compared to ICN1−/ICN2− and ICN1−/JAG1− groups. Our data revealed for the first time that NOTCH1 activation is a negative prognosticator in CLL and is not correlated to NOTCH1 and IGHV mutational status. Activation of NOTCH2 and JAGGED1 expression might also influence clinical outcomes in this group, indicating the need for further dedicated studies. The evaluation of different NOTCH network components might represent a new approach to refine CLL risk stratification.
Antidiabetic Agent DPP-4i Facilitates Murine Breast Cancer Metastasis by Oncogenic ROS-NRF2-HO-1 Axis via a Positive NRF2-HO-1 Feedback Loop
Authors: Li Rui , Zeng Xin , Yang Meihua , Xu Xiaohui , Feng Jinmei , Bao Liming , Xue Bingqian , Wang Xin , Huang Yi 
Published: May 2021

Cancer has been as one of common comorbidities of diabetes. Long-term antidiabetic treatment may potentially exert uncertain impacts on diabetic patients with cancer including breast cancer (BC). Dipeptidyl peptidase-4 inhibitors (DPP-4i) are currently recommended by the AACE as first-line hypoglycemic drugs in type 2 diabetes mellitus (T2DM). Although the safety of DPP-4i has been widely evaluated, the potential side-effects of DPP-4i in cancer metastasis were also reported and remain controversial. Here, we revealed that Saxagliptin (Sax) and Sitagliptin (Sit), two common DPP-4i compounds, potentially promoted murine BC 4T1 metastasis in vitro and in vivo under immune-deficient status. Mechanically, we observed that DPP-4i treatment induced aberrant oxidative stress by triggering ROS overproduction, as well as ROS-dependent NRF2 and HO-1 activations in BC cells, while specific inhibition of ROS, NRF2 or HO-1 activations abrogated DPP-4i-driven BC metastasis and metastasis-associated gene expression in vitro. Furthermore, ALA, a NRF2 activator significantly promoted BC metastasis in vitro and in vivo, which can be abrogated by specific HO-1 inhibition in vitro. Moreover, specific HO-1 inhibition not only reversed DPP-4i-induced NRF2 activation but also abrogated ALA-induced NRF2 activation, resulting in a decrease of metastasis-associated genes, indicating a positive-feedback NRF2-HO-1 loop. Our findings suggest that DPP-4i accelerates murine BC metastasis through an oncogenic ROS-NRF2-HO-1 axis via a positive-feedback NRF2-HO-1 loop. Therefore, this study not only offers novel insights into an oncogenic role of DPP-4i in BC progression but also provides new strategies to alleviate the dark side of DPP-4i by targeting HO-1.
Effect of Early Supplemental Formula Intervention on Body Weight and Hyperbilirubinemia in Neonates During 72 h After Birth
Authors: Zhao Lu-Lu , Lee En-Pei , Kuo Raymond Nein-Chen , Yang Stephen Shei-Dei , Huang Su-Cheng , Wu Han-Ping 
Published: May 2021

Background:The full breastfeeding may lead to insufficient milk intake of newborns and increase the rate of body weight loss (BWL). Severe BWL was generally believed as a cause of significant hyperbilirubinemia in newborn babies. The study aimed to investigate the effect if early supplemental feeding in newborns with birth weight loss at the first 3 days after birth could decrease the rate of hyperbilirubinemia 72 h of birth.Methods:A total of 395 neonates with gestational age &gt;37 weeks and birth body weight &gt;2500g were prospectively collected between 2016 and 2018. We analyzed 280 neonates with BWL rate reaching the predictive value (4.5%, 7.5%, and 8% on the first, second, third day after birth, respectively) for subsequent hyperbilirubinemia after 72 hours after birth. The enrolled cases were divided into four subgroups as interventional consecutive milk supplement for 0, 1, 2, and 3 days after birth for further analysisResults:For newborns with BWL reaching the predictive value on the first day after birth, the serum bilirubin levels were lower in the experimental group than those in the non-involved control group (p&lt; 0.05). For newborns with three consecutive days of interventional milk supplementation, the serum bilirubin levels at the 72 h after birth showed the lowest levels compared with the other sub-groups with two consecutive days and one consecutive day of interventional milk supplementation (p&lt; 0.05). Moreover, there was a significantly decreasing trend in the consecutive days of interventional milk supplementation (p&lt; 0.05).Conclusion:Newborns with BWL over 4.5% on the first day after birth receiving early intervention milk supplementation could significantly reduce serum bilirubin levels at the72 h after birth. The more days of consecutive milk supplementation after birth may lead to the lower the 72 h serum bilirubin levels. It is recommended to early and consecutive milk supplementation after birth to be an effective way in reducing serum bilirubin levels.
Interventions to Reduce Medication Dispensing, Administration, and Monitoring Errors in Pediatric Professional Healthcare Settings: A Systematic Review
Authors: Koeck Joachim A. , Young Nicola J. , Kontny Udo , Orlikowsky Thorsten , Bassler Dirk , Eisert Albrecht 
Published: May 2021

Introduction: Pediatric patients cared for in professional healthcare settings are at high risk of medication errors. Interventions to improve patient safety often focus on prescribing; however, the subsequent stages in the medication use process (dispensing, drug administration, and monitoring) are also error-prone. This systematic review aims to identify and analyze interventions to reduce dispensing, drug administration, and monitoring errors in professional pediatric healthcare settings.Methods: Four databases were searched for experimental studies with separate control and intervention groups, published in English between 2011 and 2019. Interventions were classified for the first time in pediatric medication safety according to the “hierarchy of controls” model, which predicts that interventions at higher levels are more likely to bring about change. Higher-level interventions aim to reduce risks through elimination, substitution, or engineering controls. Examples of these include the introduction of smart pumps instead of standard pumps (a substitution control) and the introduction of mandatory barcode scanning for drug administration (an engineering control). Administrative controls such as guidelines, warning signs, and educational approaches are lower on the hierarchy and therefore predicted by this model to be less likely to be successful.Results: Twenty studies met the inclusion criteria, including 1 study of dispensing errors, 7 studies of drug administration errors, and 12 studies targeting multiple steps of the medication use process. A total of 44 interventions were identified. Eleven of these were considered higher-level controls (four substitution and seven engineering controls). The majority of interventions (n = 33) were considered “administrative controls” indicating a potential reliance on these measures. Studies that implemented higher-level controls were observed to be more likely to reduce errors, confirming that the hierarchy of controls model may be useful in this setting. Heterogeneous study methods, definitions, and outcome measures meant that a meta-analysis was not appropriate.Conclusions: When designing interventions to reduce pediatric dispensing, drug administration, and monitoring errors, the hierarchy of controls model should be considered, with a focus placed on the introduction of higher-level controls, which may be more likely to reduce errors than the administrative controls often seen in practice. Trial Registration Prospero Identifier: CRD42016047127.