bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics of Cerebrospinal Fluid in Multiple Sclerosis Compared With Healthy Controls: A Pilot Study
Authors: Židó Michal , Kačer David , Valeš Karel , Svobodová Zuzana , Zimová Denisa , Štětkárová Ivana 
Published: May 2022

BackgroundMultiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading to the loss of myelin and axons. Diagnosis is based on clinical findings, MRI, and analysis of cerebrospinal fluid (CSF). CSF is an ultrafiltrate of plasma and reflects inflammatory processes in the CNS. The aim of this study was to perform metabolomics analysis of CSF in patients after the first attack of MS and healthy controls and try to find new specific analytes for MS including those potentially predicting disease activities at the onset.MethodsWe collected CSF from 19 patients (16 females, aged 19–55 years) after the first attack of clinical symptoms who fulfilled revised McDonald criteria of MS and CSF of 19 controls (16 females, aged 19–50 years). Analyses of CSF samples were provided using the high-performance liquid chromatography system coupled with a mass spectrometer with a high-resolution detector (TripleTOF 5600, AB Sciex, Canada).ResultsApproximately 130 selected analytes were identified, and 30 of them were verified. During the targeted analysis, a significant decrease in arginine and histidine and a less significant decrease in the levels of asparagine, leucine/isoleucine, and tryptophan, together with a significant increase of palmitic acid in the patient group, were found.ConclusionWe observed significant differences in amino and fatty acids in the CSF of newly diagnosed patients with MS in comparison with controls. The most significant changes were observed in levels of arginine, histidine, and palmitic acid that may predict inflammatory disease activity. Further studies are necessary to support these findings as potential biomarkers of MS.
Extruded Wheat Bran Consumption Increases Serum Short-Chain Fatty Acids but Does Not Modulate Psychobiological Functions in Healthy Men: A Randomized, Placebo-Controlled Trial
Authors: Dalile Boushra , La Torre Danique , Kalc Polona , Zoppas Francesca , Roye Chiara , Loret Chrystel , Lamothe Lisa , Bergonzelli Gabriela , Courtin Christophe M. , Vervliet Bram , Oudenhove Lukas Van , Verbeke Kristin 
Published: May 2022

BackgroundIncorporation of wheat bran (WB) into food products increases intake of dietary fiber, which has been associated with improved mood and cognition and a lower risk for psychiatric disorders such as depression, with short-chain fatty acids (SCFAs) as candidate mediators of these effects. Modifying WB using extrusion cooking increases SCFA productionin vitrorelative to unmodified WB.ObjectiveThe aim of this study was to evaluate the effects of extruded WB on psychobiological functioning and the mediating role of SCFAs.MethodsIn a randomized, triple-blind, placebo-controlled trial, 69 healthy male participants consumed 55 g of breakfast cereal containing either extruded WB or placebo daily for 28 days. At pre- and post-intervention visits, the cortisol response to experimentally induced stress was measured as a primary outcome. In addition, serum SCFAs and brain-derived neurotrophic factors were quantified as potential mediators. Secondary psychobiological outcomes included subjective stress responses, responses to experimentally induced fear, cortisol awakening response, heart rate variability, and retrospective subjective mood ratings. Intestinal permeability, fecal SCFAs, and stool consistency were measured as secondary biological outcomes.ResultsExtruded WB increased serum acetate and butyrate (p&lt; 0.05). None of the primary or secondary outcomes were affected by the intervention. Participants who consumed a placebo exhibited an increase in the percentage of fecal dry weight but did not report increased constipation. Despite these statistically significant effects, these changes were small in magnitude.ConclusionsExtruded WB consumption increased serum short-chain fatty acids but did not modulate psychobiological functions in healthy men. Effective modulation of psychobiological functions may require greater increases in SCFAs than those achieved following extruded WB consumption. Rather than attempting to induce health benefits with a single fiber-rich food, combinations of different fibers, particularly highly fermentable ones, might be needed to further increase SCFA production and uptake in the systemic circulation to observe an effect on psychobiological processes.
Identification and Validation of Novel Immune-Related Alternative Splicing Signatures as a Prognostic Model for Colon Cancer
Authors: Liu Yunze , Xu Lei , Hao Chuanchuan , Wu Jin , Jia Xianhong , Ding Xia , Lin Changwei , Zhu Hongmei , Zhang Yi 
Published: May 2022

BackgroundIndividual immune-related alternative splicing (AS) events have been found to be significant in immune regulation and cancer prognosis. However, a comprehensive analysis of AS events in cancer cells based on immune-related genes (IRGs) has not been performed, and its clinical value is unknown.MethodsColon cancer cases with AS data were obtained from TCGA, and then, we identified overall survival-related AS events (OS-ASEs) based on IRGs by univariate analyses. Using Lasso regression, multivariate Cox regression, Kaplan–Meier analysis and nomograms, we constructed an AS risk model based on the calculated risk score. Furthermore, associations of the risk score with clinical and immune features were confirmed through the Wilcoxon rank sum test, association analysis, etc. Finally, by qRT–PCR, cell coculture and CCK-8 analyses, we validated the significance of OS-ASEs in colon cancer cell lines and clinical samples.ResultsA total of 3,119 immune-related AS events and 183 OS-ASEs were identified, and 9 OS-ASEs were ultimately used to construct a comprehensive risk model for colon cancer patients. Low-risk patients had better OS and DFS rates than high risk patients. Furthermore, a high risk score corresponded to high numbers of multiple tumour-infiltrating immune cells and high expression of HLA-D region genes and immune checkpoint genes. Notably, we identified for the first time that anti-PD-L1 or anti-CTLA-4 antibodies may decrease the OS of specific colon cancer patients in the low-risk group. Additionally, the in vitro experiment validated that CD46-9652-ES and PSMC5-43011-ES are positively correlated with the infiltration of immune cells and promote the growth of colon cancer cells. CD46-9652-ES can contribute to T cell-mediated tumour cell killing. PSMC5-43011-ES was observed to induce M2 polarization of macrophages.ConclusionsThis study identified and validated immune-related prognostic AS signatures that can be used as a novel AS prognostic model and provide a novel understanding of the relationship between the immune microenvironment and clinical outcomes.
Is There Another Posterior Approach for Presacral Tumors Besides the Kraske Procedure? — A Study on the Feasibility and Safety of Surgical Resection of Primary Presacral Tumors via Transsacrococcygeal Transverse Incision
Authors: Zhao Xudong , Zhou Sixin , Liu Na , Li Peiyu , Chen Lin 
Published: May 2022

BackgroundThe aim of the present study was to explore the feasibility and safety of the surgical resection of presacral tumors via a transsacrococcygeal transverse incision.MethodsThe clinical data and prognoses of patients with presacral tumors who underwent surgery at the Chinese People’s Liberation Army (PLA) General Hospital between January 2009 and December 2018 were retrospectively reviewed and analyzed.ResultsA total of 110 patients with presacral tumors were included in this study, including 82 female patients and 28 male patients, with a female-to-male ratio of 2.9:1. A posterior approach (transsacrococcygeal transverse incision) was utilized in 105 patients, an anterior approach (transabdominal excision) was utilized in 1 patient, and a combined (posterior plus anterior) approach was utilized in 4 patients. The mean tumor size was 8.72 ± 4.28 cm. More than half of the patients (n=59/110) with presacral tumors were asymptomatic. Twenty-six pathological types were observed in our study, including 97 benign lesions and 13 malignant lesions. The intraoperative complication rate was 42.7% (n=47/110), whereas the postoperative morbidity rate was 3.6% (n=4/110). The length of hospital stay for patients treated with the posterior approach was shorter than that of patients treated with the anterior and combined approaches. After a mean follow-up of 90.13 ± 31.22 months, 11 patients had local presacral tumor recurrence, and 1 patient had distant metastasis, with a combined recurrence rate of 10.9% (n=12/110).ConclusionsThe surgical resection of primary presacral tumors via a transsacrococcygeal transverse incision is feasible and safe, with acceptable oncological therapeutic outcomes and a low postoperative morbidity rate, making it worth popularizing in clinical practice.
Ultrasound Instead of X-Ray to Diagnose Neonatal Fractures: A Feasibility Study Based on a Case Series
Authors: Liu Jing , Zhang Li , Qiu Ru-Xin 
Published: May 2022

BackgroundFracture is a common birth injury in neonates, and its diagnosis mainly depends on chest X-ray examination, while ultrasound is typically not included in the diagnostic work-up of neonatal fractures. The aim of this study was to investigate the feasibility of using ultrasound to replace X-rays for the diagnosis of fractures in newborns and to determine the ultrasound characteristics of such fractures.MethodsBedside ultrasound with an appropriate probe and scanning angle was performed on 52 newborn infants with suspected fractures based on physical examination findings, and the ultrasound results were compared with the X-ray examination results.ResultsAll 52 infants (100%) showed typical signs of fracture on ultrasound, including 46 cases of clavicle fracture, 3 cases of skull fracture, 2 cases of rib fracture, and 1 case of humerus fracture. Ultrasound was able to detect interrupted cortical continuity, displacement or angulation at the broken end, and callus formation during the recovery period. Chest X-ray examination was performed on 30 patients and identified 96.7% (29/30) of fractures, and the coincidence rate between ultrasound and X-ray was 100%. However, the sensitivity of ultrasound was higher than that of X-ray.ConclusionUltrasound diagnosis of neonatal fracture is accurate, reliable, simple, and feasible. Therefore, it can replace X-ray examinations for the routine diagnosis of common types of neonatal bone fractures.
The Role of GLI in the Regulation of Hepatic Epithelial–Mesenchymal Transition in Biliary Atresia
Authors: Siyu Pu , Junxiang Wang , Qi Wang , Yimao Zhang , Shuguang Jin 
Published: May 2022

ObjectiveTo study the regulatory role of GLI1/GLI2, a nuclear transcription factor of the Sonic hedgehog (Shh) signaling pathway, in epithelial–mesenchymal transition (EMT) related to hepatic fibrosis in patients with biliary atresia (BA).MethodsThe messenger RNA (mRNA) and protein expression levels of GLI1/GLI2, Snail/Slug, and other Shh- and EMT-related cytokines were tested in the liver tissues of BA patients and animals. Then, GLI1/GLI2 was silenced and overexpressed in mouse intrahepatic bile duct epithelial cells (mIBECs) and BA animals to investigate changes in the mRNA and protein expression of EMT key factors and liver fibrosis indicators. After silencing and overexpression of GLI1/GLI2, immunofluorescence was used to detect the expression of cytokeratin-19 (CK19) and α-smooth muscle actin (α-SMA) in mIBECs, and hematoxylin and eosin (HE) staining and Masson staining were used to observe the degree of liver fibrosis in the BA animals.ResultsCompared with the control, the mRNA and protein expression levels of GLI2, Snail, vimentin, and α-SMA were significantly increased and those of E-cadherin were significantly decreased in liver tissue from BA patients and animals. Overexpression of GLI2 increased the mRNA and protein expression levels of Snail, vimentin, and α-SMA and that of E-cadherin was significantly decreased in mIBECs and BA animals. After GLI2 silencing, the opposite pattern was observed. Immunofluorescence detection showed enhanced expression of the bile duct epithelial cell marker CK19 in mIBECs after GLI2 silencing and enhanced expression of the mesenchymal cell marker α-SMA after GLI2 overexpression. HE and Masson staining suggested that the GLI2-overexpressing group had a significantly higher degree of fibrosis.ConclusionThe Shh signaling pathway plays an important role in fibrogenesis in BA. GLI2 can significantly regulate EMT in mIBECs and livers of BA mice.
Exome Sequencing Identifies the Extremely Rare ITGAV and FN1 Variants in Early Onset Inflammatory Bowel Disease Patients
Authors: Al-Numan Huda Husain , Jan Rana Mohammed , Al-Saud Najla bint Saud , Rashidi Omran M. , Alrayes Nuha Mohammad , Alsufyani Hadeel A. , Mujalli Abdulrahman , Shaik Noor Ahmad , Mosli Mahmoud Hisham , Elango Ramu , Saadah Omar I. , Banaganapalli Babajan 
Published: May 2022

BackgroundMolecular diagnosis of early onset inflammatory bowel disease (IBD) is very important for adopting suitable treatment strategies. Owing to the sparse data available, this study aims to identify the molecular basis of early onset IBD in Arab patients.MethodsA consanguineous Arab family with monozygotic twins presenting early onset IBD was screened by whole exome sequencing (WES). The variants functional characterization was performed by a series of computational biology methods. The IBD variants were further screened in in-house whole exome data of 100 Saudi cohorts ensure their rare prevalence in the population.ResultsGenetic screening has identified the digenic autosomal recessive mode of inheritance of ITGAV (G58V) and FN1 (G313V) variants in IBD twins with early onset IBD. Findings from pathogenicity predictions, stability and molecular dynamics have confirmed the deleterious nature of both variants on structural features of the corresponding proteins. Functional biology data suggested that both genes show abundant expression in gastrointestinal tract and immune organs, involved in immune cell restriction, regulation of different immune related pathways. Data from knockout mouse models for ITGAV gene has revealed that the dysregulated expression of this gene impacts intestinal immune homeostasis. The defective ITGAV and FN1 involved in integrin pathway, are likely to induce intestinal inflammation by disturbing immune homeostasis.ConclusionsOur findings provide novel insights into the molecular etiology of pediatric onset IBD and may likely pave way in developing genomic medicine.
Antidiabetic Effect of Rehmanniae Radix Based on Regulation of TRPV1 and SCD1
Authors: Liu Ye , Zhu Ruizheng , Liu Bei , Wang Wuqing , Yang Ping , Cao Zhonglian , Yang Xiaolei , Du Wandi , Yang Qing , Liang Jingru , Hu Jiarong , Ma Guo 
Published: May 2022

Purpose: This study aimed to disclose the antidiabetic mechanisms of Rehmanniae Radix (RR).Methods: The antidiabetic effect of RR was studied in Streptozocin (STZ)–induced diabetes mellitus (DM) rats and HepG2 cells with insulin resistance (IR). Antidiabetic targets and signaling pathways of RR were confirmed by the network pharmacology and transcriptome analysis as well as HK2 cells induced by high glucose (HG).Results: After the DM rats were administrated RR extract (RRE) for 4 weeks, their body weight was 10.70 ± 2.00% higher than those in the model group, and the fasting blood glucose (FBG), AUC of the oral glucose tolerance test, and insulin sensitivity test values were 73.23 ± 3.33%, 12.31 ± 2.29%, and 13.61 ± 5.60% lower in the RRE group, respectively. When compared with the model group, an increase of 45.76 ± 3.03% in the glucose uptake of HepG2 cells with IR was seen in the RRE group. The drug (RR)–components–disease (DM)–targets network with 18 components and 58 targets was established. 331 differentially expressed genes (DEGs) were identified. TRPV1 and SCD1 were important DEGs by the intersectional analysis of network pharmacology and renal transcriptome. The TRPV1 overexpression significantly inhibited apoptosis and oxidative stress of the HK2 cells induced by HG, while SCD1 overexpression induced apoptosis and oxidative stress of the HK2 cells induced by low and high glucose. When compared to the HG group, the mRNA and protein expressions of TRPV1 in the presence of RRE (100 μg/ml) increased by 3.94 ± 0.08 and 2.83 ± 0.40 folds, respectively.Conclusion: In summary, RR displayed an inspiring antidiabetic effect by reducing FBG and IR, upregulating the mRNA and protein expressions of TRPV1, and downregulating mRNA expression of SCD1. Induction of TRPV1 and inhibition of SCD1 by RR was possibly one of its antidiabetic mechanisms.
Appropriateness of Antibiotic Prescribing in Hospitalized Children: A Focus on the Real-World Scenario of the Different Paediatric Subspecialties
Authors: Nasso Chiara , Scarfone Alessandro , Pirrotta Igor , Rottura Michelangelo , Giorgi Domenico Antonio , Pallio Giovanni , Irrera Natasha , Squadrito Violetta , Squadrito Francesco , Irrera Pierangela , Arcoraci Vincenzo , Altavilla Domenica 
Published: May 2022

Background: Antibiotics are prescribed for children both in hospital and community settings, particularly at preschool age. Italy shows a high rate of inappropriate antibiotic prescriptions which may represent a serious problem in the hospital scenario. Thus, the aim of this study was to investigate appropriateness of antibiotic prescribing in the context of different paediatric subspecialties in a hospital setting.Methods: Antibiotics prescribing was retrospectively analysed in paediatric patients (0–18 years) admitted in the emergency paediatrics, general paediatrics, paediatric nephrology and rheumatology units between January and December 2019. Patients were stratified by age in neonates, infants, toddlers, children and adolescents. Assessments were conducted by trained local assessors and appropriateness was classified as appropriate, inappropriate and not assessable.Results: Empirical antibiotics were mainly prescribed following a diagnosis of respiratory, gastrointestinal and/or urinary infection. A total of 825 antibiotic prescriptions were recorded in the three subspecialties; 462 antibiotic prescriptions (56%) out of 825 were assessed as inappropriate and 55 prescriptions (6.7%) were not assessable. Inappropriateness considerably varied within subspecialties: the risk of inappropriate antibiotic prescribing was higher in emergency paediatrics and general paediatric than in children, according to age. Ceftriaxone and clarithromycin were the most inappropriate prescribed antibiotics in the emergency paediatrics whereas amoxicillin/clavulanic acid represented the most inappropriate antibiotic prescribed in general paediatrics.Conclusion: The present data may be useful in order to reduce inappropriate antibiotic prescribing in the paediatric setting; antibiotic stewardship and clinical improvement programs in hospital paediatric care are strongly recommended.
Effects of Intermittent Hypoxia-Hyperoxia Exposure Prior to Aerobic Cycling Exercise on Physical and Cognitive Performance in Geriatric Patients—A Randomized Controlled Trial
Authors: Behrendt Tom , Bielitzki Robert , Behrens Martin , Glazachev Oleg S. , Schega Lutz 
Published: May 2022

Background: It was recently shown that intermittent hypoxic-hyperoxic exposure (IHHE) applied prior to a multimodal training program promoted additional improvements in cognitive and physical performance in geriatric patients compared to physical training only. However, there is a gap in the literature to which extent the addition of IHHE can enhance the effects of an aerobic training. Therefore, the aim of this study was to investigate the efficacy of IHHE applied prior to aerobic cycling exercise on cognitive and physical performance in geriatric patients.Methods: In a randomized, two-armed, controlled, and single-blinded trial, 25 geriatric patients (77–94 years) were assigned to two groups: intervention group (IG) and sham control group (CG). Both groups completed 6 weeks of aerobic training using a motorized cycle ergometer, three times a week for 20 min per day. The IG was additionally exposed to intermittent hypoxic and hyperoxic periods for 30 min prior to exercise. The CG followed the similar procedure breathing sham hypoxia and hyperoxia (i.e., normoxia). Within 1 week before and after the interventions, cognitive performance was assessed with the Dementia-Detection Test (DemTect) and the Clock Drawing Test (CDT), while physical performance was measured using the Timed “Up and Go” Test (TUG) and the Short-Physical-Performance-Battery (SPPB).Results: No interaction effect was found with respect to the DemTect (ηp2 = 0.02). An interaction effect with medium effect size (ηp2 = 0.08) was found for CDT performance with a higher change over time for IG (d = 0.57) compared to CG (d = 0.05). The ANCOVA with baseline-adjustment indicated between-group differences with a large and medium effect size at post-test for the TUG (ηp2 = 0.29) and SPPB (ηp2 = 0.06) performance, respectively, in favour of the IG. Within-group post-hoc analysis showed that the TUG performance was worsened in the CG (d = 0.65) and remained unchanged in the IG (d = 0.19). Furthermore, SPPB performance was increased (d = 0.58) in IG, but no relevant change over time was found for CG (d = 0.00).Conclusion: The current study suggests that an additional IHHE prior to aerobic cycling exercise seems to be more effective to increase global cognitive functions as well as physical performance and to preserve functional mobility in geriatric patients in comparison to aerobic exercise alone after a 6-week intervention period.
Perceived Dignity of Advanced Cancer Patients and Its Relationship to Sociodemographic, Clinical, and Psychological Factors
Authors: Obispo Berta , Cruz-Castellanos Patricia , Hernandez Raquel , Gil-Raga Mireia , González-Moya Manuel , Rogado Jacobo , López-Ceballos Helena , García-Carrasco Miguel , Jiménez-Fonseca Paula , Calderon Caterina 
Published: May 2022

ObjectiveLoss of dignity is one of the main reasons for wishing for an early death in patients with incurable diseases such as cancer and is strongly associated with psychological distress and loss of quality of life. The present study aims to analyze the perceived dignity of patients with advanced cancer undergoing systemic treatment and their relationship with sociodemographic, clinical, and psychological factors.MethodsA prospective, cross-sectional, multicenter study was conducted in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and Palliative Patients’ Dignity Scale, Brief Symptom Inventory, Mental Adjustment to Cancer, Functional Social Support Questionnaire, and Illness Uncertainty.ResultsA total of 508 patients were recruited between February 2020 and October 2021. Most were male, aged &gt; 65 years, with digestive tumors (41%), and metastatic disease at diagnosis. Subjects were classified as having low (56%, N = 283) or high (44%, N = 225) perceived dignity. Patients ≥ 65 years, with worse baseline status (ECOG ≥ 1), and worse estimated 18-month survival had lower levels of perceived dignity. People with lower perceived dignity scored higher for anxious preoccupation and hopelessness and lower for positive attitude. They also displayed higher levels of anxiety, depression, and somatic symptoms, greater uncertainty, and less social support.ConclusionSelf-perceived dignity in advancer cancer patients is significantly associated with psychological factors, psychological distress, uncertainty, less social support. Knowledge of these specific interactions is importance for adequate, comprehensive palliative care.