bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Prefrontal Glutamate Index Cognitive Changes in Parkinson’s Disease?
Authors: Buard Isabelle , Lopez-Esquibel Natalie , Carey Finnuella J. , Brown Mark S. , Medina Luis D. , Kronberg Eugene , Martin Christine S. , Rogers Sarah , Holden Samantha K. , Greher Michael R. , Kluger Benzi M. 
Published: April 2022

IntroductionCognitive impairment is a highly prevalent non-motor feature of Parkinson’s disease (PD). A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex (PFC), a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD.MethodsProton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD (CTL), as well as PD participants with either normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD). Ratios to Creatine (Cre) resonance were obtained for glutamate (Glu), glutamine and glutamate combined (Glx), N-acetylaspartate (NAA), myoinositol (mI), and total choline (Cho), and correlated with cognitive scores across multiple domains (executive function, learning and memory, language, attention, visuospatial function, and global cognition) administered to the PD participants only.ResultsWhen individuals retain cognitive capabilities, the presence of Parkinson’s disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction.ConclusionThese preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups.
Bioinformatics Analysis of Stem Cell circ-ASB3 Signaling Pathway and Its Affection on Glioma Biological Characteristics
Authors: Guowei Li , Yanping Jin 
Published: April 2022

ObjectiveIn our research we try to explore whether glioma stem cell containing circRNAs signal pathway could regulate glioma malignant progression and elaborate its possible mechanism.MethodsIn this study, we used biological information analysis to build an RNA regulatory network and then proceeded RT-PCR to screen target RNAs, after that we clarified the targeting relationship between circRNA-miRNA-mRNA through double luciferase gene assay, RNA pull down experiment, PCR and Western Blot. Finally we adopted RNA transfection to identify its impact on glioma cell proliferation, invasion, migration, apoptosis and cell cycle.Resultscirc-ASB3 was significantly up-regulated in glioma stem cells compared with glioma cells. The circ-ASB3/miR-543/Twist1 axis was discovered to be a possible regulatory pathway in glioma, circ-ASB3 could adsorb and targeted bind to miR-543, down-regulate miR-543 expression, thus release its targeted inhibition to Twist1. Circ-ASB3 was shown to increase glioma cell proliferation, invasion, and migration in vitro via miR-543/Twist1 axis. Meanwhile glioma cell apoptosis could be inhibited, and cell cycle arrest could be induced through this signaling pathway.Conclusioncirc-ASB3 could enhance glioma malignancy via miR-543/Twist1 axis, resulting in the discovery of new biomarkers and possible therapeutic targets for these patients.
External Validation of a Predictive Model for Acute Skin Radiation Toxicity in the REQUITE Breast Cohort
Authors: Rattay Tim , Seibold Petra , Aguado-Barrera Miguel E. , Altabas Manuel , Azria David , Barnett Gillian C. , Bultijnck Renée , Chang-Claude Jenny , Choudhury Ananya , Coles Charlotte E. , Dunning Alison M. , Elliott Rebecca M. , Farcy Jacquet Marie-Pierre , Gutiérrez-Enríquez Sara , Johnson Kerstie , Müller Anusha , Post Giselle , Rancati Tiziana , Reyes Victoria , Rosenstein Barry S. , De Ruysscher Dirk , de Santis Maria C. , Sperk Elena , Stobart Hilary , Symonds R. Paul , Taboada-Valladares Begoña , Vega Ana , Veldeman Liv , Webb Adam J. , West Catharine M. , Valdagni Riccardo , Talbot Christopher J. ,   REQUITE consortium
Published: April 2022

Background: Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve QUalITy of lifE in cancer survivors) study.Methods: Patient and treatment-related risk factors significantly associated with acute breast radiation toxicity on multivariate analysis were identified in the literature. These predictors were used to develop risk models for acute erythema and acute desquamation (skin loss) in three Radiogenomics Consortium cohorts of patients treated by breast-conserving surgery and whole breast external beam radiotherapy (n = 2,031). The models were externally validated in the REQUITE breast cancer cohort (n = 2,057).Results: The final risk model for acute erythema included BMI, breast size, hypo-fractionation, boost, tamoxifen use and smoking status. This model was validated in REQUITE with moderate discrimination (AUC 0.65), calibration and agreement between predicted and observed toxicity (Brier score 0.17). The risk model for acute desquamation, excluding the predictor tamoxifen use, failed to validate in the REQUITE cohort.Conclusions: While most published prediction research in the field has focused on model development, this study reports successful external validation of a predictive model using clinical risk factors for acute erythema following radiotherapy after breast-conserving surgery. This model retained discriminatory power but will benefit from further re-calibration. A similar model to predict acute desquamation failed to validate in the REQUITE cohort. Future improvements and more accurate predictions are expected through the addition of genetic markers and application of other modeling and machine learning techniques.
Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer
Authors: Gaudreault Mathieu , Chang David , Hardcastle Nicholas , Jackson Price , Kron Tomas , Hanna Gerard G. , Hofman Michael S. , Siva Shankar 
Published: April 2022

BackgroundBiology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT.MethodsA single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake.ResultsOf this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver.ConclusionsThe majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission tracking during BgRT.
Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients
Authors: Wan Jian , Chen Shizhen , Zhang Anqin , Liu Yiting , Zhang Yangyang , Li Qinghua , Yu Ziqi , Wan Yuwei , Yang Lei , Wang Qi 
Published: April 2022

BackgroundAdenosine-to-inosine RNA editing (ATIRE) is increasingly being used to characterize cancer. However, no studies have been conducted to identify an ATIRE signature for predicting cancer survival.MethodsBreast cancer (BRCA) samples with ATIRE profiles from The Cancer Genome Atlas were divided into training (n = 452) and internal validation cohorts (n = 311), and 197 additional BRCA patients were recruited as an external validation cohort. The ATIRE signature for BRCA overall survival (OS) and disease-free survival (DFS) were identified using forest algorithm analysis and experimentally verified by direct sequencing. An ATIRE-based risk score (AIRS) was established with these selected ATIRE sites. Significantly prognostic factors were incorporated to generate a nomogram that was evaluated using Harrell’s C-index and calibration plot for all cohorts.ResultsSeven ATIRE sites were revealed to be associated with both BRCA OS and DFS, of which four sites were experimentally confirmed. Patients with high AIRS displayed a higher risk of death than those with low AIRS in the training (hazard ratio (HR) = 3.142, 95%CI = 1.932–5.111), internal validation (HR = 2.097, 95%CI = 1.123–3.914), and external validation cohorts (HR = 2.680, 95%CI = 1.000–7.194). A similar hazard effect of high AIRS on DFS was also observed. The nomogram yielded Harrell’s C-indexes of 0.816 (95%CI = 0.784–0.847), 0.742 (95%CI = 0.684–0.799), and 0.869 (95%CI = 0.835–0.902) for predicting OS and 0.767 (95%CI = 0.708–0.826), 0.684 (95%CI = 0.605–0.763), and 0.635 (95%CI = 0.566–0.705) for predicting DFS in the three cohorts.ConclusionAIRS nomogram could help to predict OS and DFS of patients with BRCA.
Psychological Impact of the COVID-19 Pandemic on Pregnant Women
Authors: Buonsenso Danilo , Malorni Walter , Turriziani Colonna Arianna , Morini Sofia , Sbarbati Martina , Solipaca Alessandro , Di Mauro Antonio , Carducci Brigida , Lanzone Antonio , Moscato Umberto , Costa Simonetta , Vento Giovanni , Valentini Piero 
Published: April 2022

ObjectiveThe aim of this study is to assess the impact of the COVID-19 pandemic on mental health, type of delivery, and neonatal feeding of pregnant women with or without SARS-CoV-2 infection during gestation.Study DesignThe study was conducted online, and anonymous survey was distributed to mothers that delivered during the COVID-19 pandemic.ResultsThe survey was completed by 286 women, and 64 women (22.4%) had COVID-19 during pregnancy. Women that had SARS-CoV-2 infection during pregnancy or at time of delivery had a significantly higher probability of being separated from the newborn (p &lt; 0.0001) and a significantly lower probability of breastfeeding (p &lt; 0.0001). The Edinburg Postnatal Depression Scale, to assess if mothers had symptoms of postnatal depression, showed that items suggestive of postnatal depression were relatively frequent in the whole cohort. However, women with SARS-CoV-2 infection during pregnancy reported higher probability of responses suggestive of postnatal depression in eight out of 10 items, with statistically significant differences in three items.ConclusionThe COVID-19 pandemic affected the type of delivery and breastfeeding of pregnant women, particularly when they had SARS-CoV-2 infection. This, in turn, had an impact on the psychological status of the interviewed mothers, aspects that could benefit of special support.
D-dimer: The Risk Factor of Children's Severe Mycoplasma Pneumoniae Pneumonia
Authors: Qiu Juan , Ge Jin , Cao Ling 
Published: April 2022

ObjectiveMycoplasma Pneumoniae (MP) is an important cause of community-acquired pneumonia in children, which can cause serious consequences. There has been some research into predicting Severe Mycoplasma Pneumoniae Pneumonia (SMPP) primarily focused on pre-treatment time by macrolide, pre-hospital course, CRP and LDH et.al. while seldom reporting on concoagulation status. We designed this retrospective study to compare the difference between SMPP and Non-severe MPP (NSMPP) with an attempt to find the risk factors, with a special focus on concoagulation status.MethodWe performed a retrospective study of 786 MPP patients who were hospitalized from January 1, 2016 to December 31, 2018, age ranging from 28 days to 18 years old. All patients were divided into SMPP group and NSMPP group. A univariate analysis was conducted between both groups. The factors with statistical differences were included in logistic regression analysis to summarize the predictors of SMPP. Next, the predictive value of each risk factor was calculated from the receiver operating characteristic curve (ROC curve). Patients who had D-dimer records were divided into the elevated D-dimer group (D-dimer &gt; 308ug/L) and the control group (D-dimer ≤ 308ug/L), and the clinical manifestations were compared.ResultsThere was no significant difference in gender, age, pre-treatment time by macrolide, the white blood cell counts (WBC), Fibrinogen (FIB), Activated Partial Prothrombin Time (APTT), Prothrombin Time (PT) and Thrombin Time (TT) between SMPP and NSMPP. Compared with NSMPP, the pre-hospital course of SMPP was longer (P &lt; 0.05), the neutrophil ratio (N%), platelet Count (PLT), C-reactive Protein (CRP), Lactate Dehydrogenase (LDH) and D-dimer were significantly higher (P &lt; 0.01). The binary logistic regression analysis showed that the N%, PLT, CRP, LDH and D-dimer were the key predictors for SMPP, the N% &gt; 67%, OR = 3.233, PLT &gt; 445 × 109 /L, OR = 2.589, LDH &gt; 354U/L, OR = 4.335 and D-dimer level &gt; 403 ug/L, OR = 7.316. The D-dimer possessed the best predictive value. The incidence of complications such as pleural effusion, myocardial and liver damage of MPP was higher in the elevated D-dimer group than that in the control group (P &lt; 0.05).ConclusionThe N%, PLT, CRP, LDH and D-dimer were risk factors for SMPP. D-dimer was the best predictor among them. MPP patients with D-dimer &gt; 308ug/L had more complications such as pleural effusion, myocardial and liver damage. More attention should be given in the treatment for this group.
Neural Activity Correlates With Behavior Effects of Anti-Seizure Drugs Efficacy Using the Zebrafish Pentylenetetrazol Seizure Model
Authors: Milder Patrick C. , Zybura Agnes S. , Cummins Theodore R. , Marrs James A. 
Published: April 2022

Approximately 30% of patients with epilepsy do not achieve adequate seizure control through current anti-seizure drugs and treatment methods. Therefore, a critical need exists to efficiently screen anti-seizure drugs to enhance our ability to tailor treatment protocols and improve patient outcomes. The zebrafish pentylenetetrazol (PTZ) seizure model has become an increasingly popular screening paradigm for novel anti-seizure compounds. However, previous research using this model was variable due to differing experimental methods. Here, we present a method that was optimized to improve reliability and reproducibility in our laboratory using this PTZ model to develop a more robust screening of anti-seizure drugs comparing behavior and neural activity. Our behavior assay, spanning 90 min using 10 mM PTZ on 7 days post fertilization zebrafish, provides a broad window to observe anti-seizure drug efficacy. To compare our method with previously published data, we tested carbamazepine, lamotrigine, and topiramate, which have been tested in previous PTZ zebrafish assays. In addition, we assessed the candidate anti-seizure compound GS967, which has not been previously tested in the zebrafish seizure model. We examined the efficacy of anti-seizure drugs by acute administration concurrent with PTZ application and by pretreatment prior to exposure with PTZ. Pretreatment permitted us to examine potential neuroprotection and determine whether treatment time affects anti-seizure drugs’ responses. As independent validation of anti-seizure drugs’ effects, we evaluated whether the anti-seizure drug efficacy in the behavioral assay correlated with neural activity measurements, using electroencephalogram (EEG) and calcium signaling using GCaMP. There was no significant difference in the reduction of PTZ-induced seizure behavior activity between the pretreatment groups and acute treatment groups. Acute treatment with anti-seizure drugs in the EEG and GCaMP assays from 15 to 30 min post-anti-seizure drug exposure revealed consistent results between behavioral, EEG, and GCaMP assays for two of the three anti-seizure drugs. Lamotrigine only reduced neural activity (EEG and GCaMP assays). Carbamazepine, topiramate, and GS967 reduced activity in all three assays. The findings show that EEG and GCaMP assays largely correlate with the behavior findings, helping us connect physiological and behavior responses to anti-seizure drug and better assess anti-seizure drug efficacy.
Development of a Rat Model of Intra-Amniotic Inflammation via Ultrasound-Guided Administration of a Triggering Agent in the Gestational Sac to Enable Analysis of Individual Amniotic Fluid Samples
Authors: Stranik Jaroslav , Kacerovsky Marian , Sterba Martin , Andrys Ctirad , Abad Cilia , Staud Frantisek , Micuda Stanislav , Soucek Ondrej , Jacobsson Bo , Musilova Ivana 
Published: April 2022

Objectives: To develop a rat model of intra-amniotic inflammation, characterized by the concentration of interleukin-6 in the amniotic fluid, induced by an ultrasound-guided transabdominal administration of lipopolysaccharide into individual gestational sacs.Methods: An ultrasound-guided transabdominal intra-amniotic administration of lipopolysaccharide or phosphate-buffered saline (PBS) as control was performed in rats on embryonic day 18. Only accessible gestational sacs with precise recording of their positions were injected. Twenty-four hours later, individual amniotic fluid samples were collected from the gestational sacs of laparotomized animals. The gestational sacs were divided into four subgroups: (i) with lipopolysaccharide: injected gestational sacs from rats undergoing lipopolysaccharide administration; (ii) without lipopolysaccharide: non-injected gestational sacs from rats undergoing lipopolysaccharide administration; (iii) with PBS: injected gestational sacs from rats undergoing PBS administration; and (iv) without PBS: non-injected gestational sacs from rats undergoing PBS administration. The concentration of interleukin-6 in individual amniotic fluid samples was assessed using ELISA.Results: In the group of five animals receiving lipopolysaccharide, 24 (33%) and 48 (77%) gestational sacs were and were not injected, respectively. The amniotic fluid was obtained from 21 (88%) injected and 46 (95%) non-injected sacs. In the control group of five animals receiving phosphate-buffered saline, 28 (35%) and 52 (75%) gestational sacs were and were not injected, respectively. The amniotic fluid was obtained from 18 (64%) injected and 50 (96%) non-injected sacs. No labor occurred, and only one fetal death was observed in a gestational sac injected with lipopolysaccharide. Differences in concentrations of interleukin-6 in the amniotic fluid were found among the subgroups of the gestational sacs (with lipopolysaccharide: median 762 pg/ml; without lipopolysaccharide: median 35.6 pg/ml; with PBS: median 35.6 pg/ml; and without PBS: median 35.6 pg/ml; p &lt; 0.0001). Concentrations of interleukin-6 in the amniotic fluid from the gestational sacs with lipopolysaccharide were significantly higher than those in the three remaining subgroups (p &lt; 0.0001). No differences in concentrations of interleukin-6 in the amniotic fluid were identified between the three remaining subgroups.Conclusion: The ultrasound-guided transabdominal intra-amniotic administration of lipopolysaccharide with a subsequent collection and analysis of amniotic fluid samples is feasible in rats. The intra-amniotic administration of lipopolysaccharide led to the development of intra-amniotic inflammation without leading to fetal mortality or induction of labor.
Region-Dependent Increase of Cerebral Blood Flow During Electrically Induced Contraction of the Hindlimbs in Rats
Authors: Chaney Remi , Garnier Philippe , Quirié Aurore , Martin Alain , Prigent-Tessier Anne , Marie Christine 
Published: April 2022

Elevation of cerebral blood flow (CBF) may contribute to the cerebral benefits of the regular practice of physical exercise. Surprisingly, while electrically induced contraction of a large muscular mass is a potential substitute for physical exercise to improve cognition, its effect on CBF remains to be investigated. Therefore, the present study investigated CBF in the cortical area representing the hindlimb, the hippocampus and the prefrontal cortex in the same anesthetized rats subjected to either acute (30 min) or chronic (30 min for 7 days) electrically induced bilateral hindlimb contraction. While CBF in the cortical area representing the hindlimb was assessed from both laser doppler flowmetry (LDFCBF) and changes in p-eNOSSer1177 levels (p-eNOSCBF), CBF was evaluated only from changes in p-eNOSSer1177 levels in the hippocampus and the prefrontal cortex. The contribution of increased cardiac output and increased neuronal activity to CBF changes were examined. Stimulation was associated with tachycardia and no change in arterial blood pressure. It increased LDFCBF with a time- and intensity-dependent manner as well as p-eNOSCBF in the area representing the hindlimb. By contrast, p-eNOSCBF was unchanged in the two other regions. The augmentation of LDFCBF was partially reduced by atenolol (a ß1 receptor antagonist) and not reproduced by the administration of dobutamine (a ß1 receptor agonist). Levels of c-fos as a marker of neuronal activation selectively increased in the area representing the hindlimb. In conclusion, electrically induced bilateral hindlimb contraction selectively increased CBF in the cortical area representing the stimulated muscles as a result of neuronal hyperactivity and increased cardiac output. The absence of CBF changes in cognition-related brain regions does not support flow-dependent neuroplasticity in the pro-cognitive effect of electrically induced contraction of a large muscular mass.