bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis
Authors: Sullivan Gemma , Galdi Paola , Borbye-Lorenzen Nis , Stoye David Q. , Lamb Gillian J. , Evans Margaret J. , Skogstrand Kristin , Chandran Siddharthan , Boardman James P. 
Published: September 2021

IntroductionPreterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.PopulationFor objective one 59 term infants [mean gestational age (GA) 39+4 (37+3 to 42+0)] and 55 preterm infants [mean GA29+0(23+3 to 32+0)] with umbilical cord samples available were included; for objective two we studied 96 preterm infants [mean GA29+1(23+2 to 32+0)] for whom placental histology and postnatal blood samples were available.MethodsPlacental histopathology was used to identify reaction patterns indicative of HCA, and a customized immunoassay of 24 inflammatory markers and trophic proteins selected to reflect the perinatal immune response was performed on umbilical cord blood in term and preterm participants and postnatal day 5 blood in the preterm group.ResultsThe umbilical cord blood immune profile classified gestational age category with 86% accuracy (95% CI 0.78-0.92), p-value=1.242x10-14. Pro-inflammatory proteins IL-6, MCP-1 and CRP were elevated in the cord blood of preterm infants whilst BDNF, C3, C9, IL-18, MMP-9 and RANTES were decreased, compared to infants born at term. In preterm infants, exposure to HCA was associated with elevations in 8 immune proteins on postnatal day 5 (BDNF, C3, C5a, C9, IL-8, MCP-1, MIP-1β and MMP-9) when compared to preterm infants who were not exposed.ConclusionPreterm birth is associated with a distinct immune profile in umbilical cord blood and preterm infants exposed to HCA with evidence of a fetal inflammatory response have specific alterations in immune function that are apparent on day 5 of postnatal life.
Running Behind “POPO”—Impact of Predictors of Poor Outcome for Treatment Stratification in Pediatric Crohn's Disease
Authors: de Laffolie Jan , Zimmer Klaus-Peter , Sohrabi Keywan , Hauer Almuthe Christina 
Published: September 2021

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease.Methods: CD patients (1–18 years) registered in CEDATA-GPGE® (2004–2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties.Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission &gt;1 year (Odd Ratio (OR) 1.49 [1.07–2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89–131.62], p &lt; 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39–33.58], p &lt; 0.001; OR 2.56 [1.58–4.15], p &lt; 0.001, respectively). Positive Predictive Value for lack of sustained remission was &gt;60% for patients with initial growth failure, persistent or stricturing/penetrating disease.Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.
Delivery of miR-26a Using an Exosomes-Based Nanosystem Inhibited Proliferation of Hepatocellular Carcinoma
Authors: Mahati Shaya , Fu Xiangjun , Ma Xuexian , Zhang Hua , Xiao Lei 
Published: September 2021

Background: MicroRNA (abbreviated miRNA)-based treatment holds great promise for application as clinical antitumor therapy, but good carriers for delivery of the miRNA drug are lacking. Exosomes secreted by mesenchymal stem cells (MSCs) have proved to be safe, and exogenously modified exosomes may potentially represent an excellent drug delivery vehicle.Methods: In this study, we designed a delivery nano system using single-stranded variable fragment (scFv)-modified exosomes derived from human cord blood MSCs. Genetic engineering technology was used to obtain anti-Glypican 3 (GPC3) scFv-modified exosomes, which were then loaded with miR-26a mimics through electroporation.Results: Results of electron microscopy and dynamic light scattering indicated that the diameter of the drug-carrying exosomes was about 160 nm. Furthermore, anti-GPC3 scFv-modified exosomes effectively delivered miR-26a to GPC3-positive hepatocellular carcinoma cells, thereby inhibiting cell proliferation and migration by regulating the expression of downstream target genes of miR-26a. The exosomes-based nano system displayed favorable anti-tumor effect in vivo with no obvious side effects.Conclusion: Our data provided a new perspective for the use of exosome delivery systems for miRNA-based antitumor therapy.
The Effect and Mechanism of Cholesterol and Vitamin B12 on Multi-Domain Cognitive Function: A Prospective Study on Chinese Middle-Aged and Older Adults
Authors: Wang Lijing , Liu Kuo , Zhang Xiaona , Wang Yushan , Liu Wen , Wang Tao , Hao Ling , Ju Mengwei , Xiao Rong 
Published: September 2021

Background: Nutrients are associated with cognitive function, but limited research studies have systematically evaluated on multi-domain cognitive function. The aim of this study was to investigate the effect and mechanism of specific nutrient on multi-domain cognitive function, and provide nutrition guidance for improving cognitive function.Methods: Participants were selected based on a multicenter prospective study on middle-aged and older adults in China. Global cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Nutrients intake was assessed according to food frequency questionnaire and China Food Composition Database, and principal component analysis was performed to extract nutrient patterns. Associations between specific nutrients and cognitive function were assessed using log-binomial regression. Restricted cubic spline was used to illustrate the dose-response relationship of nutrients with multi-domain cognitive function. Mediation analysis was used to determine the mechanism of nutrients in cognitive function.Results: Four nutrient patterns were identified (vitamin-mineral, protein-carbohydrate, fatty acid-vitamin E, and cholesterol-vitamin B12), and only a nutrient pattern rich in cholesterol and vitamin B12 was found associated with cognitive function (RR = 0.891, 95%CI = 0.794–0.999). In multi-domain cognitive function, dietary cholesterol and vitamin B12 were related to better performance of visual memory function (P = 0.034, P = 0.02). In dose-response relationship, it suggested a U-shaped association between vitamin B12 and MMSE (P = 0.02) within a certain range.Conclusions: Dietary intake rich in cholesterol and vitamin B12 was associated with better cognitive function, and vitamin B12 had a U-shaped dose-response relation with MMSE. Thus, ensuring moderate cholesterol and vitamin B12intake may be an advisable strategy to improve cognitive function in middle-aged and older adults.Clinical Trial Registration: EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610
Vascular Diameters as Predictive Factors of Recanalization Surgery Outcomes in Internal Carotid Artery Occlusion
Authors: Yan Chengrui , Wang Jiaru , Guo Ruohan , Jin Weitao , Zhao Yang , Wang Rong 
Published: September 2021

Background: Revascularization surgery sometimes can achieve recanalization in patients with internal carotid artery occlusion (ICAO). High-resolution vessel wall magnetic resonance imaging (HRVWI) is a feasible technique to give detailed characteristics of the vessel wall, which may help to identify patients that carry higher success rates and more suitable for revascularization surgery.Objective: To examine the association between HRVWI characteristics of ICAO and the success rate of revascularization surgery in ICAO patients.Methods: We conducted a retrospective analysis of 31 ICAO recanalization patients enrolled from October 2017 to May 2019. The clinical data of patients and lesions were collected and analyzed.Results: A total of 31 ICAO patients were enrolled in this study. No significant differences were found between recanalization success and recanalization failure groups with regard to occlusion length, distal end of the occluded segment, and the treatment applied. The ipsilateral-to-contralateral diameter ratios (I/C ratios) of C1 or C2 and the diameter of C7 were positively related to recanalization success. A two-factor predictive model was constructed, and the I/C ratio of C2 &lt; 0.86 and the diameter of C7 &lt; 1.75mm were separately assigned 1 point. The ICAO patients who scored 0, 1, or 2 points had a risk of 5.6% (1/18), 55.6% (5/9), or 100% (4/4) to fail in the recanalization.Conclusions: The I/C ratios of C1 or C2 and the diameter of C7 are predictive factors of a revascularization surgery success in ICAO patients. A risk stratification model involving C2 and C7 was constructed for future clinical applications.
Application of High-Resolution Flat Detector Computed Tomography in Stent Implantation for Intracranial Atherosclerotic Stenosis
Authors: Li Tengfei , Wang Yuting , Ma Ji , Levitt Michael , Mossa-Basha Mahmud , Shi Chengcheng , Ran Yuncai , Ren Jianzhuang , Han Xinwei , Zhu Chengcheng 
Published: September 2021

ObjectiveTo evaluate the utility of high-resolution flat-detector computed tomography (HR-FDCT) compared with conventional flat-detector computed tomography (FDCT) for stent placement in symptomatic intracranial atherosclerotic stenosis (ICAS).MethodsWe retrospectively reviewed the clinical data of 116 patients with symptomatic ICAS who underwent stent implantation. Images were acquired using conventional FDCT [voxel size = 0.43 mm (isotropic)] and HR-FDCT [voxel size = 0.15 mm (isotropic)]. Immediately after stent deployment, dual-volume three-dimensional (3D) fusion images were obtained from 3D digital subtraction angiography (DSA) and HR-FDCT. The image quality for stent visualization was graded from 0 to 2 (0: not able to assess; 1: limited, but able to assess; 2: clear visualization), and the stent-expansion status (“full,” “under-expanded” or “poor apposition”) was recorded.ResultsA total of 116 patients with symptomatic ICAS were treated successfully using 116 stents (58 NeuroformTM EZ, 42 EnterpriseTM, and 16 ApolloTM). The mean pre-stent stenosis was 80.5 ± 6.4%, which improved to 20.8 ± 6.9% after stenting. Compared with FDCT, HR-FDCT improved visualization of the fine structures of the stent to improve the image quality that significantly (mean score: 1.63 ± 0.60 vs. 0.41 ± 0.59, P &lt; 0.001). In 19 patients, stent under-expansion (n = 11) or poor apposition (n = 8) was identified by HR-FDCT but not by conventional FDCT. After balloon dilatation, stent malapposition was shown to have improved on HR-FDCT. None of the 19 patients with stent malapposition experienced short-term complications during hospitalization or had in-stent stenosis at 6-month follow-up.ConclusionHigh-resolution flat-detector computed tomography (HR-FDCT) improves visualization of the fine structures of intracranial stents deployed for symptomatic ICAS compared with that visualized using conventional FDCT. High-resolution flat-detector computed tomography improves assessment of stent deployment and could reduce the risk of complications.
PRG5 Knockout Precipitates Late-Onset Hypersusceptibility to Pilocarpine-Induced Juvenile Seizures by Exacerbating Hippocampal Zinc Signaling-Mediated Mitochondrial Damage
Authors: Wang Dandan , Jin Mei-fang , Li Lili , Liu Yueying , Sun Yuxiao , Ni Hong 
Published: September 2021

IntroductionEpileptogenesis is understood as the plastic process that produces a persistent reorganization of the brain’s neural network after a precipitating injury (recurrent neonatal seizures, for instance) with a latent period, finally leading to neuronal hyperexcitability. Plasticity-related genes (PRGs), also known as lipid phosphate phosphatase-related proteins (PLPPRs), are regulators of mitochondrial membrane integrity and energy metabolism. This study was undertaken to determine whether PRG5 gene knockout contributes to the delayed hypersensitivity induced by developmental seizures and the aberrant sprouting of hippocampal mossy fibers, and to determine whether it is achieved through the mitochondrial pathway. Here, we developed a “twist” seizure model by coupling pilocarpine-induced juvenile seizures with later exposure to penicillin to test the long-term effects of PRG5 knockout on seizure latency through comparison with wild-type (WT) mice. Hippocampal mossy fiber sprouting (MFS) was detected by Timm staining. In order to clarify the mechanism of the adverse reactions triggered by PRG5 knockout, hippocampal HT22 neuronal cultures were exposed to glutamate, with or without PRG5 interference. Mitochondrial function, oxidative stress indicators and zinc ion content were detected.ResultsPRG5 gene knockout significantly reduced the seizure latency, and aggravated the lowered seizure threshold induced by developmental seizures. Besides, knockout of the PRG5 gene reduced the MFS scores to a certain extent. Furthermore, PRG5 gene silencing significantly increases the zinc ion content in hippocampal neurons, impairs neuronal activity and mitochondrial function, and exacerbates glutamate-induced oxidative stress damage.ConclusionIn summary, PRG5 KO is associated with significantly greater hypersusceptibility to juvenile seizures in PRG5(–/–) mice compared with WT mice. These effects may be related to the hippocampal zinc signaling. The effects do not appear to be related to changes in MFS because KO mice with juvenile seizures had the shortest seizure latencies but exhibited less MFS than WT mice with juvenile seizures.
Supplementation of Kiwifruit Polyphenol Extract Attenuates High Fat Diet Induced Intestinal Barrier Damage and Inflammation via Reshaping Gut Microbiome
Authors: Yuan Minlan , Chen Xiao , Su Tianxia , Zhou Yan , Sun Xiaohong 
Published: September 2021

Background: Impaired intestinal integrity and barrier function is associated with various diseases, including inflammatory bowel disease and metabolic syndrome. In recent years, plant-derived polyphenols have attracted much attention on regulating intestinal barrier function. Kiwifruit was recorded as a traditional Chinese medicine which can treat gastrointestinal diseases, but the mechanism was still unclear. In this study we investigated the effects of kiwifruit polyphenol extracts (KPE) on high fat diet induced intestinal permeability and its possible mechanism.Results: Dietary supplementation of KPE with 50 or 100 mg/kg bw could inhibit the increase of intestinal permeability caused by HFD and promote the expression of tight junction protein (Claudin-1, Occludin and ZO-1). From microbial diversity and RT-PCR, KPE administration reshaping gut microbiome, the relative abundance of Lactobacillus and Bifidobacterium were increased, and the relative abundance of Clostridium and Desulfovibrionaceae were decreased. The changes in microbe may influence intestinal inflammatory status. Then the expression of TLRs and cytokines were detected. KPE supplementation showed anti-inflammatory effect, the expression of IL-10 was increased and the expression of TLR-2, TLR-4, TNF-α and IL-1β were decreased. Correlation analysis indicated that the expression of tight junction protein was negative correlation with TLR-2, TLR-4, TNF-α and IL-1β expression, but positively correlated with Bacteroidete, Bifidobacterium and IL-10 expression; the expression of Bacteroidete, Lactobacillusand and Bifidobacterium were negative correlation with TLR4, TNF-α, and IL-1β expression.Conclusion: KPE treatment relieve the intestinal damage caused by HFD, which was related to the regulation of Bacteroidete, Lactobacillusand, and Bifidobacterium expression and inhibit intestinal inflammation. KPE could be a functional component for preventing gut damage and its related disease.
Brief Research Report: Estimation of the Protein Digestibility-Corrected Amino Acid Score of Defatted Walnuts
Authors: Lackey Kimberly A. , Fleming Stephen A. 
Published: September 2021

Introduction: Walnuts are considered a good source of essential fatty acids, which is unique among tree nuts. Walnuts are also composed of about 10–15% protein, but the quality of this protein has not been evaluated. Pistachios and almonds have been evaluated for their protein content using a protein digestibility-corrected amino acid score (PDCAAS), but it is unclear how the quality of protein in walnuts relates to that in other commonly consumed tree nuts. The objective of this study was to substantiate the protein quality of walnuts by determining their PDCAAS.Methods: A small, 10-day dietary intervention trial was conducted using male Sprague-Dawley rats (n = 8, 4 per group) with two diets: a nitrogen-free diet and a diet containing protein exclusively from defatted walnuts. Feed intake and fecal output of nitrogen were measured to estimate the true protein digestibility, and the amino acid compositions of walnuts compared to child and adult populations were used to calculate amino acid scores (AAS) and PDCAAS.Results: The true protein digestibility score of raw walnuts was calculated to be 86.22%. Raw walnuts contained 15.6 g protein/g walnut with AAS of 0.45 and 0.63 for children aged 6 months to 3 years and 3–10 years, respectively. For each population, a PDCAAS of 39 and 46% was calculated, respectively, using a protein conversion constant of 5.30. Using a protein constant of 6.25, a PDCAAS of 39% (6 months - 3 years) or 46% (3-10 years) was calculated.Conclusions: This is the first known assessment of the PDCAAS of walnuts. Like almonds, they appear to have a low-to-moderate score, indicating they are not a quality source of protein.
The Ratio of Preoperative Serum Biomarkers Predicts Prognosis in Patients With Oral Squamous Cell Carcinoma
Authors: Ding Meng , Song Yuxian , Jing Junyan , Tian Mei , Ding Liang , Li Qiang , Zhou Chongchong , Dong Heng , Ni Yanhong , Mou Yongbin 
Published: September 2021

BackgroundDynamic changes in circulating immune-inflammatory cells have been regarded as simple and convenient prognostic biomarkers in various cancers. However, studies on the prognostic values of their ratios in oral squamous cell carcinoma (OSCC) remain limited.Materials and MethodsA total of 493 OSCC patients were included in the present study. Here, we investigated the prognostic values of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white blood cell ratio (NWR), and lymphocyte-to-white blood cell ratio (LWR) in OSCC. The correlations of the NLR, LMR, NWR, and LWR with clinicopathological characteristics were statistically analyzed using the Chi-square test, Kaplan-Meier curves, and univariate and multivariate Cox regression models.ResultKaplan-Meier analyses revealed that OSCC patients with a high LMR and low NWR had prolonged overall survival (OS, P&lt;0.001) and disease-free survival (DFS, P&lt;0.001 and P=0.003, respectively), but there were no significant differences in metastasis-free survival (MFS, P=0.053 and P=0.052, respectively). In contrary, a high NLR and low LWR were associated with poor OS (P&lt;0.001 and P=0.0016, respectively), DFS (P=0.0014 and 0.0012, respectively) and MFS (P=0.021 and 0.008, respectively). Additionally, Cox multivariate analyses showed that the LMR was an independent prognostic factor for both OS (P=0.007) and DFS (P=0.017), while the LWR was an independent prognostic factor for MFS (P=0.009).ConclusionPreoperative NLR, LMR, NWR, and LWR in the peripheral blood are significant prognostic factors for OSCC and might be helpful in predicting OSCC progression.
Adverse Events as a Potential Clinical Marker of Antitumor Efficacy in Ovarian Cancer Patients Treated With Poly ADP-Ribose Polymerase Inhibitor
Authors: Ni Jing , Cheng Xianzhong , Zhou Rui , Zhao Qian , Xu Xia , Guo Wenwen , Gu Hongyuan , Chen Chen , Chen Xiaoxiang 
Published: September 2021

BackgroundPARP inhibitor (PARPi) is an important progress in ovarian cancer treatment. The available evidence suggests that BRCA mutation and homologous recombination deficiency (HRD) are effective biological markers for PARPi. Here we investigated the relationship between adverse events (AEs) and efficacy of PARPi in ovarian cancer patients.MethodsSeventy-eight patients with ovarian cancer patients underwent Olaparib and Niraparib from July 2018 to July 2020 were analyzed. AEs were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Chi-square test or fisher exact tests was performed to observe the association between categorical variables. Logistic regression analysis was conducted to investigate the independent variables for disease control response (DCR). Progression-free survival (PFS) was compared between AEs variables by log-rank test.ResultsPatients with AEs in the first one week had a higher DCR compared with those after one week (86.11% versus 60.98%, p=0.013). Patients with serious AEs (SAEs) had a significantly higher DCR (81.40% versus 60.60%, p=0.045). There were associations between anemia and DCR in both occurrence (79.63% versus 56.52%, p=0.037) and grade (100% versus 73.17%, p=0.048). The median PFS of patients with hematological toxicity was longer than that of patients with no-hematological toxicity (30 versus 20 weeks, p=0.047). Patients with hematological toxicity within four weeks had prolonged median PFS than those with hematological toxicity after four weeks (40 versus 22 weeks, p=0.003).ConclusionsThe early presence of AEs and SAEs in hematological toxicity of PARPi were related to the antitumor efficacy, which might be a valid and easily measurable clinical marker in ovarian cancer patients.