bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhouse Bridging Thrombolysis Is Associated With Improved Functional Outcome in Patients With Large Vessel Occlusion Stroke: Findings From the German Stroke Registry
Authors: Maier Ilko L. , Leha Andreas , Badr Mostafa , Allam Ibrahim , Bähr Mathias , Jamous Ala , Hesse Amelie , Psychogios Marios-Nikos , Behme Daniel , Liman Jan 
Published: June 2021

Background: Endovascular treatment (EVT) for large vessel occlusion stroke (LVOS) is highly effective. To date, it remains controversial if intravenous thrombolysis (IVT) prior to EVT is superior compared with EVT alone. The aim of our study was to specifically address the question, whether bridging IVT directly prior to EVT has additional positive effects on reperfusion times, successful reperfusion, and functional outcomes compared with EVT alone.Methods: Patients with LVOS in the anterior circulation eligible for EVT with and without prior IVT and direct admission to endovascular centers (mothership) were included in this multicentric, retrospective study. Patient data was derived from the German Stroke Registry (an open, multicenter, and prospective observational study). Outcome parameters included groin-to-reperfusion time, successful reperfusion [defined as a Thrombolysis in Cerebral Infarction (TICI) scale 2b-3], change in National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and mortality at 90 days.Results: Of the 881 included mothership patients with anterior circulation LVOS, 486 (55.2%) received bridging therapy with i.v.-rtPA prior to EVT, and 395 (44.8%) received EVT alone. Adjusted, multivariate linear mixed effect models revealed no difference in groin-to-reperfusion time between the groups (48 ± 36 vs. 49 ± 34 min; p = 0.299). Rates of successful reperfusion (TICI ≥ 2b) were higher in patients with bridging IVT (fixed effects estimate 0.410, 95% CI, 0.070; 0.750, p = 0.018). There was a trend toward a higher improvement in the NIHSS during hospitalization [ΔNIHSS: bridging-IVT group 8 (IQR, 9.8) vs. 4 (IQR 11) points in the EVT alone group; fixed effects estimate 1.370, 95% CI, −0.490; 3.240, p = 0.149]. mRS at 90 days follow-up was lower in the bridging IVT group [3 (IQR, 4) vs. 4 (IQR, 4); fixed effects estimate −0.350, 95% CI, −0.680; −0.010, p = 0.041]. There was a non-significantly lower 90 day mortality in the bridging IVT group compared with the EVT alone group (22.4% vs. 33.6%; fixed effects estimate 0.980, 95% CI −0.610; 2.580, p = 0.351). Rates of any intracerebral hemorrhage did not differ between both groups (4.1% vs. 3.8%, p = 0.864).Conclusions: This study provides evidence that bridging IVT might improve rates of successful reperfusion and long-term functional outcome in mothership patients with anterior circulation LVOS eligible for EVT.
Altered Relationship Between Heart Rate Variability and fMRI-Based Functional Connectivity in People With Epilepsy
Authors: Kassinopoulos Michalis , Harper Ronald M. , Guye Maxime , Lemieux Louis , Diehl Beate 
Published: June 2021

Background: Disruptions in central autonomic processes in people with epilepsy have been studied through evaluation of heart rate variability (HRV). Decreased HRV appears in epilepsy compared to healthy controls, suggesting a shift in autonomic balance toward sympathetic dominance; recent studies have associated HRV changes with seizure severity and outcome of interventions. However, the processes underlying these autonomic changes remain unclear. We examined the nature of these changes by assessing alterations in whole-brain functional connectivity, and relating those alterations to HRV.Methods: We examined regional brain activity and functional organization in 28 drug-resistant epilepsy patients and 16 healthy controls using resting-state functional magnetic resonance imaging (fMRI). We employed an HRV state-dependent functional connectivity (FC) framework with low and high HRV states derived from the following four cardiac-related variables: 1. RR interval, 2. root mean square of successive differences (RMSSD), 4. low-frequency HRV (0.04–0.15 Hz; LF-HRV) and high-frequency HRV (0.15–0.40 Hz; HF-HRV). The effect of group (epilepsy vs. controls), HRV state (low vs. high) and the interactions of group and state were assessed using a mixed analysis of variance (ANOVA). We assessed FC within and between 7 large-scale functional networks consisting of cortical regions and 4 subcortical networks, the amygdala, hippocampus, basal ganglia and thalamus networks.Results: Consistent with previous studies, decreased RR interval (increased heart rate) and decreased HF-HRV appeared in people with epilepsy compared to healthy controls. For both groups, fluctuations in heart rate were positively correlated with BOLD activity in bilateral thalamus and regions of the cerebellum, and negatively correlated with BOLD activity in the insula, putamen, superior temporal gyrus and inferior frontal gyrus. Connectivity strength in patients between right thalamus and ventral attention network (mainly insula) increased in the high LF-HRV state compared to low LF-HRV; the opposite trend appeared in healthy controls. A similar pattern emerged for connectivity between the thalamus and basal ganglia.Conclusion: The findings suggest that resting connectivity patterns between the thalamus and other structures underlying HRV expression are modified in people with drug-resistant epilepsy compared to healthy controls.
Globus Pallidus Internus Deep Brain Stimulation for Dystonic Opisthotonus in Adult-Onset Dystonia: A Personalized Approach
Authors: Tambirajoo Kantharuby , Furlanetti Luciano , Samuel Michael , Ashkan Keyoumars 
Published: June 2021

IntroductionDystonic opisthotonus is defined as a backward arching of the neck and trunk, which ranges in severity from mild backward jerks to life-threatening prolonged severe muscular spasms. It can be associated with generalized dystonic syndromes or, rarely, present as a form of axial truncal dystonia. The etiologies vary from idiopathic, genetic, tardive, hereditary-degenerative, or associated with parkinsonism. We report clinical cases of dystonic opisthotonus associated with adult-onset dystonic syndromes, that benefitted from globus pallidus internus (GPi) deep brain stimulation (DBS).MethodsClinical data from patients with dystonic syndromes who underwent comprehensive medical review, multidisciplinary assessment, and tailored medical and neurosurgical managements were prospectively analyzed. Quantification of dystonia severity pre- and postoperatively was performed using the Burke-Fahn-Marsden Dystonia Rating Scale and quantification of overall pain severity was performed using the Visual Analog Scale.ResultsThree male patients, with age of onset of the dystonic symptoms ranging from 32 to 51 years old, were included. Tardive dystonia, adult-onset dystonia-parkinsonism and adult-onset idiopathic axial dystonia were the etiologies identified. Clinical investigation and management were tailored according to the complexity of the individual presentations. Although they shared common clinical features of adult-onset dystonia, disabling dystonic opisthotonus, refractory to medical management, was the main indication for GPi-DBS in all patients presented. The severity of axial dystonia ranged from disturbance of daily function to life-threatening truncal distortion. All three patients underwent bilateral GPi DBS at a mean age of 52 years (range 48–55 years), after mean duration of symptoms prior to DBS of 10.7 years (range 4–16 years). All patients showed a rapid and sustained clinical improvement of their symptoms, notably of the dystonic opisthotonos, at postoperative follow-up ranging from 20 to 175 months. In some, the ability to resume activities of daily living and reintegration into the society was remarkable.ConclusionAdult-onset dystonic syndromes predominantly presenting with dystonic opisthotonus are relatively rare. The specific nature of dystonic opisthotonus remains a treatment challenge, and thorough investigation of this highly disabling condition with varying etiologies is often necessary. Although patients may be refractory to medical management and botulinum toxin injection, Globus pallidus stimulation timed and tailored provided symptomatic control in this cohort and may be considered in other carefully selected cases.
No Difference in Arousal or Cognitive Demands Between Manual and Partially Automated Driving: A Multi-Method On-Road Study
Authors: Lohani Monika , Cooper Joel M. , Erickson Gus G. , Simmons Trent G. , McDonnell Amy S. , Carriero Amanda E. , Crabtree Kaedyn W. , Strayer David L. 
Published: June 2021

IntroductionPartial driving automation is not always reliable and requires that drivers maintain readiness to take over control and manually operate the vehicle. Little is known about differences in drivers’ arousal and cognitive demands under partial automation and how it may make it difficult for drivers to transition from automated to manual modes. This research examined whether there are differences in drivers’ arousal and cognitive demands during manual versus partial automation driving.MethodWe compared arousal (using heart rate) and cognitive demands (using the root mean square of successive differences in normal heartbeats; RMSSD, and Detection Response Task; DRT) while 39 younger (M= 28.82 years) and 32 late-middle-aged (M= 52.72 years) participants drove four partially automated vehicles (Cadillac, Nissan Rogue, Tesla, and Volvo) on interstate highways. If compared to manual driving, drivers’ arousal and cognitive demands were different under partial automation, then corresponding differences in heart rate, RMSSD, and DRT would be expected. Alternatively, if drivers’ arousal and cognitive demands were similar in manual and partially automated driving, no difference in the two driving modes would be expected.ResultsResults suggest no significant differences in heart rate, RMSSD, or DRT reaction time performance between manual and partially automated modes of driving for either younger or late-middle-aged adults across the four test vehicles. A Bayes Factor analysis suggested that heart rate, RMSSD, and DRT data showed extreme evidence in favor of the null hypothesis.ConclusionThis novel study conducted on real roads with a representative sample provides important evidence of no difference in arousal and cognitive demands. Younger and late-middle-aged motorists who are new to partial automation are able to maintain arousal and cognitive demands comparable to manual driving while using the partially automated technology. Drivers who are more experienced with partially automated technology may respond differently than those with limited prior experience.
Psychosocial Determinants of Vegetable Intake Among Nepalese Young Adults: An Exploratory Survey
Authors: Pandey Sujita , Budhathoki Mausam , Yadav Dipendra Kumar 
Published: June 2021

Background: Adequate intake of vegetables facilitates a healthy lifestyle. However, the majority of Nepalese young adults consume inadequate amount of vegetables per day.Objectives: We explored psychosocial determinants of daily intake of two or more servings of vegetables among Nepalese young adults using attitude, social influence, and self-efficacy (ASE) as a theoretical framework, extended with measures of habit and self-identity as additional constructs.Methods/Participants: A cross-sectional study through a web-based questionnaire survey was conducted among 461 Nepalese young adults aged 18–35 years old. Participants were recruited through convenience (snowball) sampling. A factor-based partial least square structural equation modelling was used for analysis.Results: The findings indicated that attitudes (β = 0.09, p = 0.029), social influence (β = 0.17, p &lt; 0.001), habit (β = 0.24, p &lt; 0.001) and self-identity (β = 0.30, p &lt; 0.001) were significant factors influencing intention to eat two or more servings of vegetables per day. Further, self-efficacy (β = 0.10, p = 0.011), habit (β = 0.08, p = 0.034), diet (β = −0.10, p = 0.014), and place of residence (β = 0.11, p = 0.007) significantly influenced behaviour to eat two or more servings of vegetables per day. However, self-efficacy (β = 0.07, p = 0.062) did not significantly influence intention and self-identity (β = 0.06, p = 0.083), age (β = −0.02, p = 0.328), gender (β = 0.02, p = 0.350), and body mass index (β = −0.04, p = 0.209) did not significantly influence behaviour to eat two or more servings of vegetables per day.Conclusion: The study shows that attitudes, social influence, habit, and self-identity were significant factors influencing intention to eat two or more servings of vegetables per day. Further, self-efficacy and habit significantly influenced behaviour to eat two or more servings of vegetables per day. However, self-efficacy did not significantly influence intention and self-identity did not significantly influence behaviour to eat two or more servings of vegetables per day.
The Correlation Between SPP1 and Immune Escape of EGFR Mutant Lung Adenocarcinoma Was Explored by Bioinformatics Analysis
Authors: Zheng Yi , Hao Shiying , Xiang Cheng , Han Yaguang , Shang Yanhong , Zhen Qiang , Zhao Yiyi , Zhang Miao , Zhang Yan 
Published: June 2021

BackgroundImmune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.MethodsWe compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.ResultsSPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.ConclusionSPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics.
Integrative Multi-Omics Analysis of Identified NUF2 as a Candidate Oncogene Correlates With Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer
Authors: Chen Mengqing , Li Shangkun , Liang Yuling , Zhang Yue , Luo Dan , Wang Wenjun 
Published: June 2021

BackgroundLung cancer is one of the most common malignant tumors and the leading causes of cancer-related deaths worldwide. As a component of the nuclear division cycle 80 complex, NUF2 is a part of the conserved protein complex related to the centromere. Although the high expression of NUF2 has been reported in many different types of human cancers, the multi-omics analysis in non-small cell lung cancer (NSCLC) of NUF2 remains to be elucidated.MethodsIn this analysis, NUF2 expression difference analysis in non-small cell lung cancer was evaluated by Oncomine, TIMER, GEO, and TCGA database. And the prognosis analysis of NUF2 based on Kaplan-Meier was performed. R language was used to analyze the differential expression genes, functional annotation and protein-protein interaction (PPI). GSEA analysis of differential expression genes was also carried out. Mechanism analysis about exploring the characteristic of NUF2, multi-omics, and correlation analysis was carried out using UALCAN, cBioportal, GEPIA, TIMER, and TISIDB, respectively.ResultsThe expression of NUF2 in NSCLC, both lung adenocarcinoma (LUAD) and squamous lung cancer (LUSC), was significantly higher than that in normal tissues. The analysis of UALCAN database samples proved that NUF2 expression was connected with stage and smoking habits. Meanwhile, the overall survival curve also validated that high expression of NUF2 has a poorer prognosis in NSCLC. GO, KEGG, GSEA, subcellular location from COMPARTMENTS indicated that NUF2 may regulate the cell cycle. Correlation analysis also showed that NUF2 was mainly positively associated with cell cycle and tumor-related genes. NUF2 altered group had a poorer prognosis than unaltered group in NSCLC. Immune infiltration analysis showed that the NUF2 expression mainly have negatively correlation with immune cells and immune subtypes in LUAD and LUSC. Furthermore, quantitative PCR was used to validate the expression difference of NUF2 in LUAD and LUSC.ConclusionOur findings elucidated that NUF2 may play an important role in cell cycle, and significantly associated with tumor-related gene in NSCLC; we consider that NUF2 may be a prognostic biomarkers in NSCLC.
N6-Methyladenosine Associated Silencing of miR-193b Promotes Cervical Cancer Aggressiveness by Targeting CCND1
Authors: Huang Chunxian , Liang Jinxiao , Lin Shaodan , Wang Dongyan , Xie Qingsheng , Lin Zhongqiu , Yao Tingting 
Published: June 2021

ObjectiveCervical cancer is a frequently encountered gynecological malignancy as a major contributor to cancer-related deaths in women. This study focuses on how miR-193b promotes cervical cancer aggressiveness as well as the role of m6A in miR-193b silencing.MethodsCervical cancer samples and the matching adjacent normal cervical tissues were used to determine the significance of miR-193b in cervical cancer. The CCK-8 assay, cell cycle analysis, qRT-PCR, Western blot assay, IHC, RIP, and xenograft models were utilized to explore the impact of miR-193b in cervical cancer and how m6A regulates miR-193b expression. Luciferase reporter assays, qRT-PCR, and Western blotting were enlisted to study the interaction between miR-193b and CCND1.ResultsOur study suggested that lower miR-193b expressions were strongly linked to more advanced cervical cancer stages and the presence of deeper stromal invasion. miR-193b functions as a tumor suppressor that is regulated by m6A methylation in cervical tumors. METTL3 modulates miR-193b mature process in an m6A-dependent manner. Reintroduction of miR-193b profoundly inhibits tumorigenesis of cervical cancer cells both in vivo and in vitro through CCND1 targeting.Conclusionsm6A associated downregulation of miR-193b promotes cervical cancer aggressiveness by targeting CCND1.
Telehealth for Children With Epilepsy Is Effective and Reduces Anxiety Independent of Healthcare Setting
Authors: Klotz Kerstin Alexandra , Borlot Felippe , Scantlebury Morris H. , Payne Eric T. , Appendino Juan Pablo , Schönberger Jan , Jacobs Julia 
Published: June 2021

Objectives: The use of telemedicine has grown exponentially as an alternative to providing care to patients with epilepsy during the pandemic. We investigated the impact of the current pandemic among children with epilepsy from two distinct pediatric epilepsy centers. We also compared perceptions among those who received telemedicine against those who did not.Methods: We developed a questionnaire and invited families followed in Freiburg, Germany, and Calgary, Alberta, Canada, to participate during the initial 9 months of the pandemic. The survey contained 32 questions, 10 of which were stratified according to telemedicine exposure.Results: One hundred twenty-six families (80 in Freiburg, 46 in Calgary) participated, and 40.3% received telemedicine care. Most children (mean age 10.4 years, SD 5.1) had chronic epilepsy but poorly controlled seizures. Negative impacts were reported by 36 and 65% of families who had to reschedule appointments for visits and diagnostics, respectively. Nearly two-thirds of families reported no change in seizure frequency, while 18.2% reported either worsening or improvement of seizures. Although most families did not note behavioral changes, 28.2% reported behavior worsening. Families who received telemedicine care had a statistically significant reduction of parental self-reported anxiety level after virtual visits compared to those who did not experience telemedicine. Families with telemedicine consultations were more likely to consider future virtual care (84 vs. 65.2% of those without), even after the pandemic. Patient data safety, easy access to specialized services, and consistency with the same healthcare provider were graded as important in both centers, while a shorter waiting time was most relevant in Calgary.Conclusion: In our cohort, some children with epilepsy experienced increased seizures and worsening behavior during the first 9 months of the current pandemic. In addition, our data suggest that telemedicine might reduce parental anxiety symptoms, and families who experienced telehealth were more positive and open to similar appointments in the future.
Fecal High-Mobility Group Box 1 as a Marker of Early Stage of Necrotizing Enterocolitis in Preterm Neonates
Authors: Vitali Roberta , Terrin Gianluca , Palone Francesca , Laudadio Ilaria , Cucchiara Salvatore , Boscarino Giovanni , Di Chiara Maria , Stronati Laura 
Published: June 2021

Introduction:An early diagnosis of necrotizing enterocolitis (NEC), a major gastrointestinal emergency in preterm newborns, is crucial to improve diagnostic approach and prognosis. We evaluated whether fecal high-mobility group box protein 1 (HMGB1) may early identify preterms at risk of developing NEC.Materials and Methods:A case-control study including neonates admitted at the Neonatal Intensive Care Unit (NICU) of the Sapienza University Hospital “Umberto I” in Rome, from July 2015 to December 2016. Stool samples obtained from cases (preterm newborns with NEC) and controls (newborns without NEC) were collected at the enrolment (T0) and within 7–14 days after the first sample collection (T1). HMGB1, extracted and measured with western blot, was reported as densitometry units (DUS).Results:HMGB1 levels in 30 cases (n= 28—Bell stage 1,n= 2 Bell stage 2) were higher [T0: 21,462 DUS (95% CI, 16,370–26,553 DUS)—T1: 17,533 DUS (95% CI, 13,052–22,014 DUS)] than in 30 preterm controls [T0: 9,446 DUS (95% CI, 6,147–12,746 DUS)—T1: 9,261 DUS (95% CI, 5,126–13,396 DUS),p&lt; 0.001). Preterm newborns showed significant higher levels of HMGB1 (15,690 DUS (95% CI, 11,929–19,451 DUS)] in comparison with 30 full-term neonates with birth weight &gt;2,500 g [6,599 DUS (95% CI, 3,141–10,058 DUS),p= 0.003]. Multivariate analysis showed that the risk of NEC was significantly (p= 0.012) related to the HMGB1 fecal levels at T0.Conclusions:We suggest fecal HMGB1 as a reliable marker of early NEC in preterm neonates. This study supports further investigation on the role of fecal HMGB1 assessment in managing preterm newborns at risk of NEC. Further studies are advocated to evaluate diagnostic accuracy of this marker in more severe forms of the disease.