bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic Inflammation Increases the Susceptibility to Levodopa-Induced Dyskinesia in 6-OHDA Lesioned Rats by Targeting the NR2B-Medicated PKC/MEK/ERK Pathway
Authors: Yan Aijuan , Song Lu , Zhang Yu , Wang Xijin , Liu Zhenguo 
Published: February 2021

Background: The long-term administration of levodopa (L-dopa), the gold-standard treatment for Parkinson's disease (PD), is irreparably associated with L-dopa-induced dyskinesia (LID), which dramatically affects the quality of life of patients. However, the underlying molecular mechanisms of how LID exacerbates remain unknown. Neuroinflammation in the striatum plays an active role in LID. These findings prompt an investigation of non-neuronal mechanisms of LID. This study will examine the effects of systemic inflammation in the development and progression of LID.Methods: To evaluate the possible influence of systemic inflammation in the appearance of LID, the PD rats received an intraperitoneal (IP) injection of various concentrations of lipopolysaccharides (LPS, 1, 2, and 5 mg/kg) or saline. One day later, these PD rats started to receive daily treatment with L-dopa (6 mg/kg) along with benserazide (6 mg/kg) or saline for 21 days, and dyskinesia was evaluated at several time points. Moreover, the activation of microglia and astrocytes and the molecular changes in NR2B and mGLUR5 signaling pathways were measured.Results: We found that systemic inflammatory stimulation with LPS exacerbated the intensity of abnormal involuntary movements (AIMs) induced by L-dopa treatment in 6-hydroxydopamine (6-OHDA) lesioned rats. The LPS injection activated the gliocytes and increased the levels of proinflammatory cytokines in the striatum in LID rats. The PD rats that received the LPS injection showed the overexpression of p-NR2B and NR2B, as well as activated PKC/MEK/ERK and NF-κB signal pathways in response to the L-dopa administration. On the contrary, clodronate-encapsulated liposomes (Clo-lipo), which could suppress the inflammatory response induced by peripheral LPS injection, improved behavioral dysfunction, inhibited neuroinflammation, prevented NR2B overexpression, and decreased the phosphorylation of PKC/MEK/ERK and NF-κB signaling pathways.Conclusion: This study suggests that systemic inflammation, by exacerbating preexisting neuroinflammation and facilitating NR2B subunit activity, may play a crucial role in the development of LID. The administration of Clo-lipo restores the effects of LPS and decreases the susceptibility to LID in 6-OHDA lesioned rats.
Label-Free Liquid Chromatography–Mass Spectrometry Proteomic Analysis of Urinary Identification in Diabetic Vascular Dementia in a Han Chinese Population
Authors: Chen Ruijuan , Yi Yuanjing , Xiao Wenbiao , Zhong Bowen , Shu Yi , Zhang Le , Zeng Yi 
Published: February 2021

Objective:This study aimed to identify potential diagnostic biomarkers of diabetic vascular dementia (DVD) and unravel the underlying mechanisms using mass spectrometry (MS).Methods:Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was applied to urine samples from four groups, including 14 patients with vascular dementia (VD), 22 patients with type 2 diabetes mellitus (T2DM), 12 patients with DVD, and 21 normal controls (NCs). Searching the MS data by Proteome Discoverer software (ThermoFisher Scientific; Waltham, MA, USA), protein abundances were analyzed qualitatively and quantitatively and compared between these groups. Combining bioinformatics analysis using Gene Ontology (GO), pathway crosstalk analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network analysis using STRING, and literature searching, the differentially expressed proteins (DEPs) of DVD can be comprehensively judged and were further quantified by receiver operating characteristic (ROC) curve methods.Results:The proteomic findings showed quantitative changes in patients with DVD compared to patients with NC, T2DM, and VD groups; among 4,744 identified urine proteins, 1,222, 1,152, and 1,180 proteins displayed quantitative changes unique to DVD vs. NC, T2DM, and VD, respectively, including 481 overlapped common DEPs. Then, nine unique proteins [including HP, SERPIND, ATP5PB, VNN2, ALDH3A1, U2AF2, C6, A0A5C2GRG5 (no name), and A0A5C2FZ29 (no name)] and two composite markers (CM) (A0A5C2GRG5+U2AF2 and U2AF2+C6) were confirmed by a ROC curve method.Conclusion:This study provided an insight into the potential pathogenesis of DVD and elucidated a method for early detection.
Identification of MicroRNA–Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy
Authors: Li Zheng , Ma Yixun , Zhou Fengjuan , Jia Xiao , Zhan Jingjing , Tan Huachao , Wang Xu , Yang Tiantong , Liu Quan 
Published: February 2021

Background: Dysregulated expression of microRNAs and potassium channels have been reported for their contributions to seizure onset. However, the microRNA–potassium channel gene interactions in traumatic brain injury-induced post-traumatic epilepsy (PTE) remain unknown.Methods: PTE was induced in male rats by intracranial injection with ferrous chloride (0.1 mol/L, 1 μl/min) at the right frontal cortex. Electroencephalography was recorded at 60 min, as well as day 1, 7, and 30, and the behavioral seizures were assessed before injection and at different time points after injection. Rats were killed on day 30 after injection. The right frontal cortex samples were collected and subjected to high throughput messenger RNA (mRNA) and microRNA sequencing. A network of differentially expressed potassium channel mRNAs and microRNAs was constructed using OryCun2.0 and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The differential mRNA and microRNA expressions were verified using quantitative real-time-PCR. The microRNA–mRNA was subject to the Pearson correlation analysis.Results: A PTE rat model was successfully established, as evidenced by behavioral seizures and epileptiform discharges on electroencephalography in PTE rats compared with sham rats. Among the 91 mRNAs and 40 microRNAs that were significantly differentially expressed in the PTE rat brain, 4 mRNAs and 10 microRNAs were associated with potassium channels. Except for potassium calcium-activated channel subfamily N member 2, the other three potassium channel mRNAs were negatively correlated with seven microRNAs. These microRNA–mRNA pairs were enriched in annotations and pathways related to neuronal ion channels and neuroinflammation. Quantitative real-time-PCR and correlation analysis verified negative correlations in miR-449a-5p-KCNH2, miR-98-5p-KCNH2, miR-98-5p-KCNK15, miR-19b-3p-KCNK15, and miR-301a-3p-KCNK15 pairs.Conclusion: We identified microRNA–potassium channel mRNA interactions associated with PTE, providing potential diagnostic markers and therapeutic targets for PTE.
Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis
Authors: Zhang Chen , Yang Qing 
Published: February 2021

BackgroundThe prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression.MethodsPubMed, EMBASE and Cochrane Library databases were searched. The associations between PD-L1 expression status and prognosis [overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), cancer-specific survival (CSS) or disease-free survival (DFS)], clinical parameters [FIGO stage, lymph node metastasis (LNM), tumor size, infiltration depth, lymphovascular space invasion (LVSI) or grade] and response to anti-PD-1/PD-L1 treatment [objective response rate (ORR)] were analyzed by hazard ratios (HR) or relative risks (RR).ResultsFifty-five studies were enrolled. Overall, high PD-L1 expression was not significantly associated with OS, PFS, RFS, CSS and DFS of gynecological cancers. However, subgroup analysis of studies with reported HR (HR = 1.27) and a cut-off value of 5% (HR = 2.10) suggested that high PD-L1 expression was correlated with a shorter OS of gynecological cancer patients. Further sub-subgroup analysis revealed that high PD-L1 expressed on tumor-infiltrating immune cells (TICs) predicted a favorable OS for ovarian (HR = 0.72), but a poor OS for cervical cancer (HR = 3.44). PD-L1 overexpression was also correlated with a lower OS rate in non-Asian endometrial cancer (HR = 1.60). High level of PD-L1 was only clinically correlated with a shorter PFS in Asian endometrial cancer (HR = 1.59). Furthermore, PD-L1-positivity was correlated with LNM (for overall, ovarian and endometrial cancer expressed on tumor cells), advanced FIGO stage (for overall, ovarian cancer expressed on tumor cells, endometrial cancer expressed on tumor cells and TICs), LVSI (for overall and endometrial cancer expressed on tumor cells and TICs), and increasing infiltration depth/high grade (only for endometrial cancer expressed on TICs). Patients with PD-L1-positivity may obtain more benefit from anti-PD-1/PD-L1 treatment than the negative group, showing a higher ORR (RR = 1.98), longer OS (HR = 0.34) and PFS (HR = 0.61).ConclusionOur findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.
Clinicopathological Characteristics and Treatment Strategies of Triple-Negative Breast Cancer Patients With a Survival Longer than 5 Years
Authors: Xie Ning , Xu Ying , Zhong Ying , Li Junwei , Yao Herui , Qin Tao 
Published: February 2021

PurposeTriple-negative breast cancer (TNBC) is characterized by high malignancy and a poor prognosis. Patients with TNBC who survive longer than 5 years represent a unique portion of the population. This study aimed to analyze the clinicopathological features, explore prognostic factors, and evaluate treatment options for these patients.MethodsA total of 24,943 TNBC patients were enrolled from the national Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2016. The patients were divided into three groups: group 1, survival time &lt;3 years; group 2, 3–5 years; and group 3, survival time ≥5 years. The overall survival (OS) and breast cancer cause-specific survival (BCSS) were primarily assessed in this study. A propensity score analysis was used to avoid bias caused by the data selection criteria. We used a Cox hazard ratio analysis to determine prognostic factors, which were selected as nomogram parameters to develop a model for predicting patient survival.ResultsPatients who survived longer than 5 years were more likely to be younger than 55 years, Caucasian, and exhibit a lower AJCC stage, N stage, distant metastasis, lymph node (LN) involvement, and tumor size than those with a shorter survival time (p &lt; 0.05). The multivariable Cox regression analysis showed that age, race, tumor size, LN status, and chemotherapy were independent prognostic factors. Subgroup analyses for patients with tumors ≤20 mm displayed a superior OS and BCSS for breast-conserving surgery (BCS) not treated with a mastectomy. BCS provided at least an equivalent prognosis to a mastectomy in patients with tumors larger than 20 mm. A nomogram with a C-index of 0.776 (95% confidence interval: 0.767–0.785) was developed to predict the 3- and 5-year survival probability for the patients with TNBC.ConclusionA localized surgical approach may represent a superior choice for TNBC patients with a survival time longer than 5 years. Our study indicated that age, race, tumor size, LN status, and chemotherapy were independent prognostic factors. A prognostic nomogram directly quantified patient risk and was better able to predict long-term survival in TNBC patients.
Neoadjuvant Cabozantinib in an Unresectable Locally Advanced Renal Cell Carcinoma Patient Leads to Downsizing of Tumor Enabling Surgical Resection: A Case Report
Authors: Bilen Mehmet A. , Jiang James F. , Jansen Caroline S. , Brown Jacqueline T. , Harik Lara R. , Sekhar Aarti , Kissick Haydn , Maithel Shishir K. , Kucuk Omer , Carthon Bradley , Master Viraj A. 
Published: February 2021

IntroductionCabozantinib (XL-184) is a small molecule inhibitor of the tyrosine kinases c-Met, AXL, and VEGFR2 that has been shown to reduce tumor growth, metastasis, and angiogenesis. After the promising results from the METEOR and CABOSUN trials, cabozantinib was approved for use in the first- and second-line setting in patients with advanced RCC. Previously, targeted therapies have been used in the neoadjuvant setting for tumor size reduction and facilitating nephrectomies. The increased response rates with cabozantinib in metastatic renal cell carcinoma (mRCC), along with the other neoadjuvant TKI data, strongly support an expanded role for cabozantinib in the neoadjuvant setting.Case DescriptionWe report on a 59-year-old gentleman presenting with an unresectable 21.7 cm left renal cell carcinoma (RCC) with extension to soft tissue and muscles of the thoracic cage, psoas muscle, posterior abdominal wall, tail of pancreas, splenic flexure of colon, and inferior margin of spleen. Presurgical, neoadjuvant systemic therapy with cabozantinib was initiated for 11 months in total. Initially after 2 months of cabozantinib, magnetic resonance imaging (MRI) revealed a significant reduction (44.2%) in tumor diameter from 21.7 to 12.1 cm with decreased extension into adjacent structures. After 11 months total of cabozantinib, the corresponding MRI showed grossly stable size of the tumor and significant resolution of invasion of adjacent structures. After washout of cabozantinib, radical resection, including nephrectomy, was successfully performed without any major complications, either intra-operative or perioperative. Negative margins were achieved.ConclusionsThis is a report of neoadjuvant cabozantinib downsizing a tumor and enabling surgical resection in this patient with locally advanced RCC. Our findings demonstrate that neoadjuvant cabozantinib to facilitate subsequent surgical resection may be a feasible option for patients presenting with unresectable RCC.
Episodic Autobiographical Memory in Adults With Autism Spectrum Disorder: An Exploration With the Autobiographical Interview
Authors: Coutelle Romain , Goltzene Marc-André , Canton Marie , Campiglia-Sabourin Mélodie , Rabot Juliette , Bizet Éric , Schoenberger Marie , Berna Fabrice , Danion Jean-Marie 
Published: February 2021

Introduction: The literature has provided contradictory results regarding the status of episodic memory in autism spectrum disorder (ASD). This might be explained by methodological differences across studies. In the present one, the well-recommended Autobiographical Interview was used in which important aspects of episodic memory were assessed, namely, the number and richness of phenomenological memory details, before and after a retrieval support.Method: Twenty-five well-documented adults with ASD without Intellectual Disability (nine women) and 25 control participants were included and asked to recall six specific autobiographical events. The number and richness of details were assessed globally and for five categories of details (perceptual/sensory, temporal, contextual, emotional, and cognitive), firstly before and then after a specific cueing phase consisting in a series of specific questions to elicit more precise memory details.Results: Cumulatively, from the spontaneous recall to the cueing phase, the number of internal details was lower in ASD individuals compared to controls, but this difference was relevant only after the specific cueing procedure and observed only for contextual details. In contrast, no relevant group difference was observed during spontaneous recall. The detail richness was not impaired in ASD throughout the Autobiographical Interview procedure.Conclusion: Our results speak against a clear impairment of episodicity of autobiographical memory in ASD individuals. They thus challenge previous ones showing both a reduced specificity and episodicity of autobiographical memory in this population and call for further studies to get a better understanding on the status of episodic autobiographical memory in ASD.
COVID-19 Pandemic: Demographic Predictors of Self-Isolation or Self-Quarantine and Impact of Isolation and Quarantine on Perceived Stress, Anxiety, and Depression
Authors: Nkire Nnamdi , Mrklas Kelly , Hrabok Marianne , Gusnowski April , Vuong Wesley , Surood Shireen , Abba-Aji Adam , Urichuk Liana , Cao Bo , Greenshaw Andrew J. , Agyapong Vincent I. O. 
Published: February 2021

Introduction: With the sudden onset and global dispersal of the SARS-CoV-2 virus, many nations including Canada attempted to reduce spread of the resultant COVID-19 syndrome with self-isolation and quarantine, while seeking a cure or vaccine for this disease. Understanding impacts of self-isolation and self-quarantine on stress, anxiety, and depression will help us to mitigate these issues through appropriate development of mental health services.Methods: The sample was drawn from individuals who self-subscribed to Text4Hope, a service that delivers text messages based on a cognitive behavioral therapy framework. Text4Hope was developed to support Albertans during the COVID-19 pandemic. Subscribers were asked for demographic information and if they had to self-isolate or self-quarantine during the pandemic via a survey link. Mental health was assessed using the validated instruments: Perceived Stress Scale (PSS), Generalized Anxiety Disorder-7 item scale (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9). Descriptive statistics and Chi-Square test results were derived using Statistical Package for Social Sciences (SPSS) version-26.Results: 6,041 of 32,805 Text4Hope subscribers (18.4%) completed the survey. Of these respondents, 19.2% had self-isolated or self-quarantined in Alberta as of March 31, 2020 during the COVID-19 pandemic. Post-hoc analysis using adjusted residuals suggested that individuals aged 60 years of age or older, and retirees had a higher likelihood of self-isolation or self-quarantine, compared to respondents with other age or employment characteristics. One-week prevalence rates for self-reported measures of moderate to high stress, likely Generalized Anxiety Disorder (GAD), and likely Major Depressive Disorder (MDD) were 84.9, 46.7, and 41.4%, respectively. Respondents who had to self-isolate or self-quarantine during the COVID-19 pandemic were significantly more likely to present with moderate to high stress, significant anxiety symptomatology, and significant depressive symptomatology.Conclusions: Older age and employment status were significantly associated with the likelihood of self-isolation or self-quarantine. We found elevated self-reported levels of anxiety and depression associated with self-reported COVID-19 pandemic-related self-isolation and self-quarantine activity. These findings have mental health implications both during and after the pandemic and demonstrate the need for greater focus on psychological complications of self-isolation and self-quarantine, and development of optimal ways to manage these pandemic consequences.
Correlation of Demographics, Healthcare Availability, and COVID-19 Outcome: Indonesian Ecological Study
Authors: Wirawan Gede Benny Setia , Januraga Pande Putu 
Published: February 2021

Objective: To analyze the correlation between demographic and healthcare availability indicators with COVID-19 outcome among Indonesian provinces.Methods: We employed an ecological study design to study the correlation between demographics, healthcare availability, and COVID-19 indicators. Demographic and healthcare indicators were obtained from the Indonesian Health Profile of 2019 by the Ministry of Health while COVID-19 indicators were obtained from the Indonesian COVID-19 website in August 31st 2020. Non-parametric correlation and multivariate regression analyses were conducted with IBM SPSS 23.0.Results: We found the number of confirmed cases and case growth to be significantly correlated with demographic indicators, especially with distribution of age groups. Confirmed cases and case growth was significantly correlated (p &lt; 0.05) with population density (correlation coefficient of 0.461 and 0.491) and proportion of young people (−0.377; −0.394). Incidence and incidence growth were correlated with ratios of GPs (0.426; 0.534), hospitals (0.376; 0.431), primary care clinics (0.423; 0.424), and hospital beds (0.472; 0.599) per capita. For mortality, case fatality rate (CFR) was correlated with population density (0.390) whereas mortality rate was correlated with ratio of hospital beds (0.387). Multivariate analyses found confirmed case independently associated with population density (β of 0.638) and demographic structure (−0.289). Case growth was independently associated with density (0.763). Incidence growth was independently associated with hospital bed ratio (0.486).Conclusion: Pre-existing inequality of healthcare availability correlates with current reported incidence and mortality rate of COVID-19. Lack of healthcare availability in some provinces may have resulted in artificially low numbers of cases being diagnosed, lower demands for COVID-19 tests, and eventually lower case-findings.
Early Life Modifiable Exposures and Their Association With Owner Reported Inflammatory Bowel Disease Symptoms in Adult Dogs
Authors: Hemida Manal , Vuori Kristiina A. , Moore Robin , Anturaniemi Johanna , Hielm-Björkman Anna 
Published: February 2021

Background: Inflammatory bowel disease (IBD) is an idiopathic multifactorial disease in humans and dogs, usually assigned to the interactions between genes, gut microbiota, diet, environment, and the immune system. We aimed to investigate the modifiable early life exposures associated with IBD in dogs.Materials and Methods: The study data was extracted from the validated owner-reported DogRisk food frequency questionnaire. This was a cross-sectional questionnaire-based study that tested 21 different early life dietary and environmental, demographic and genetic variables for their association with IBD or not, in adult dogs. A total of 7,015 dogs participated in this study. The study covered early life periods; prenatal, neonatal, early, and late postnatal periods. Two feeding patterns, a non-processed meat-based diet (NPMD) and an ultra-processed carbohydrate-based diet (UPCD) were studied. Data was analyzed using logistic regression analysis with a backward stepwise deletion.Results: From the final models we found that the NPMD during early and late postnatal periods were significantly associated with lower IBD risk later in life. The UPCD during the same periods was associated with a higher risk of IBD incidence. Also, the maternal diet during the neonatal period showed a non-significant trend of lower IBD risk in the offspring with the NPMD and a higher IBD risk with the UPCD. Additionally, the normal body weight of puppies during the first 6 months of age was associated with a lower risk of IBD in adulthood while, slim puppies associated significantly with IBD in adulthood. From the non-modifiable background variables, we identified the maternal history of IBD as the strongest risk factor for later incidence of IBD. Furthermore, male dogs were twice as likely to develop IBD as female dogs were.Conclusions: It is reassuring for owners to know that they themselves can have an impact on their dog's health. A high-fat, low-carbohydrate NPMD exposure during early life, and a normal body condition in puppyhood were significantly associated with less IBD in adult dogs. The opposite was true for UPCD exposure and abnormal body condition score in 6 month old puppies.