bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Dimensional Display of Wang’s Lymph Node Map Using Virtual Bronchoscopic Navigation System
Authors: Lan Fen , Yue Yaling , Shen Hong , Shen Hui , Wang Qiyuan , Yu Xiujing , Chen Laijuan , Li Qin , Wang Kopen , Liu Qinghua , Xia Yang 
Published: June 2021

Background:Transbronchial needle aspiration (TBNA) is a classical technique for diagnosing mediastinal-hilar lymph node enlargement. However, the diagnostic value of conventional TBNA (cTBNA) is limited in small lymph nodes.Methods:Here, we generated an innovative multi-dimensional virtual lymph node map on top of Wang’s lymph node map using a Lungpoint Virtual Bronchoscopic Navigation System.Results:The virtual bronchoscopic navigation (VBN) system was combined with computed tomography (CT) images to generate extrabronchial, endobronchial, sagittal, coronal as well as horizontal views of the 11 intrathoracic lymph node stations and their adjacent tissues and blood vessels. We displayed the specific puncture site of each lymph node station. The 11 stations were divided into four groups: right mediastinal stations, left mediastinal stations, central mediastinal stations and hilar stations.Conclusion:The VBN system provides a precise view of the intrabronchial landmarks, which may increase the diagnostic accuracy of intrathoracic lymph node adenopathy and assist bronchoscopists with practicing TBNA.
Network Mapping of Time to Antithrombotic Therapy Among Patients With Ischemic Stroke and Transient Ischemic Attack (TIA)
Authors: Phan Thanh G. , Clissold Benjamin , Singhal Shaloo , Ly John Van , Lim Andy , Vuong Jason , Ho Stella , Matley Chelsea , Kooblal Talvika , Ma Henry 
Published: June 2021

Background: There is emphasis on timely administration of thrombolysis and clot retrieval but not antithrombotic therapy within 48 h for ischemic stroke (frequency of 64% in Australia and 97% in North America). We planned to assess the time metrics and variables associated with delaying antithrombotics (antiplatelet and anticoagulant therapy) administration.Methods: This was a retrospective study at Monash Health over 12 months in 2015. We plotted the cumulative event and mapped the key drivers (dimensionless variable Shapley value/SV) of antithrombotics.Results: There were 42 patients with transient ischemic attack/TIA and 483 with ischemic stroke [mean age was 71.8 ± 15.4; 56.0% male; nil by mouth (NBM) 74.5 and 49.3% of patients received “stat” (immediate and one off) dose antithrombotics]. The median time to imaging for the patients who did not have stroke code activated was 2.3 h (IQR 1.4–3.7), from imaging to dysphagia screen was 14.6 h (IQR 6.2–20.3), and from stopping NBM to antithrombotics was 1.7 h (IQR 0–16.5). TIA patients received antithrombotics earlier than those with ischemic stroke (90.5 vs. 86.5%, p = 0.01). Significant variables in regression analysis for time to antithrombotics were time to dysphagia screen (β 0.20 ± 0.03, SV = 3.2), nasogastric tube (β 19.8 ± 5.9, SV = −0.20), Alteplase (β 8.6 ± 3.6, SV = −1.9), stat dose antithrombotic (β −18.9 ± 2.9, SV = −10.8) and stroke code (β −5.9 ± 2.5, SV = 2.8). The partial correlation network showed that the time to antithrombotics increased with delay in dysphagia screen (coefficient = 0.33) and decreased if “stat” dose of antithrombotics was given (coefficient = −0.32).Conclusion: The proportion of patients receiving antithrombotics within 48 h was higher than previously reported in Australia but remained lower than the standard achieved in North American hospitals. Our process map and network analysis show avenues to shorten the time to antithrombotic.
Endovascular Treatment of Acute Ischemic Stroke in Clinical Practice: Analysis of Workflow and Outcome in a Tertiary Care Center
Authors: Weissenborn Karin , Gruber Sam , Grosse Gerrit M. , Gabriel Maria , Schuppner Ramona , Worthmann Hans , Abu-Fares Omar , Götz Friedrich 
Published: June 2021

Background and Purpose: Pre- and intra-hospital workflow in mechanical recanalization of large cervicocephalic arteries in patients with acute ischemic stroke still needs optimization. In this study, we analyze workflow and outcome in our routine care of stroke patients undergoing mechanical thrombectomy as a precondition for such optimization.Methods: Processes of pre- and intra-hospital management, causes of treatment delay, imaging results (Alberta Stroke Program Early Computed Tomography Score, localization of vessel occlusion), recanalization (modified thrombolysis in cerebral infarction score), and patient outcome (modified Rankin scale at discharge and at the end of inpatient rehabilitation) were analyzed for all patients who underwent mechanical thrombectomy between April 1, 2016, and September 30, 2018, at our site.Results: Finally, data of 282 patients were considered, of whom 150 (53%) had been referred from external hospitals. Recanalization success and patient outcome were similar to randomized controlled thrombectomy studies and registries. Delay in treatment occurred when medical treatment of a hypertensive crisis, epileptic fits, vomiting, or agitation was mandatory but also due to missing prenotification of the hospital emergency staff by the rescue service, multiple mode or repeated brain imaging, and transfer from another hospital. Even transfer from external hospitals located within a 10-km radius of our endovascular treatment center led to a median increase of the onset-to-groin time of ~60 min.Conclusion: The analysis revealed several starting points for an improvement in the workflow of thrombectomy in our center. Analyses of workflow and treatment results should be carried out regularly to identify the potential for optimization of operational procedures and selection criteria for patients who could benefit from endovascular treatment.
Computed Tomography Based Score of Early Ischemic Changes Predicts Malignant Infarction
Authors: Bechstein Matthias , Meyer Lukas , Breuel Silke , Faizy Tobias D. , Hanning Uta , van Horn Noel , McDonough Rosalie , Fiehler Jens , Broocks Gabriel 
Published: June 2021

Background and Purpose:Identification of ischemic stroke patients at high risk of developing life-threatening malignant infarction at an early stage is critical to consider more rigorous monitoring and further therapeutic measures. We hypothesized that a score consisting of simple measurements of visually evident ischemic changes in non-enhanced CT (NEMMI score) predicts malignant middle cerebral artery (MCA) infarctions (MMI) with similar diagnostic power compared to other baseline clinical and imaging parameters.Methods:One hundred and nine patients with acute proximal MCA occlusion were included. Fifteen (13.8%) patients developed MMI. NEMMI score was defined using the sum of the maximum diameter (anterior-posterior plus medio-lateral) of the hypoattenuated lesion in baseline-CT multiplied by a hypoattenuation factor (3-point visual grading in non-enhanced CT, no/subtle/clear hypoattenuation = 1/2/3). Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis were used to calculate the predictive values of the NEMMI score, baseline clinical and other imaging parameters.Results:The median NEMMI score at baseline was 13.6 (IQR: 11.6–31.1) for MMI patients, and 7.7 (IQR: 3.9–11.2) for patients with non-malignant infarctions (p&lt; 0.0001). Based on ROC curve analysis, a NEMMI score &gt;10.5 identified MMI with good discriminative power (AUC: 0.84, sensitivity/specificity: 93.3/70.7%), which was higher compared to age (AUC: 0.76), NIHSS (AUC: 0.61), or ischemic core volume (AUC: 0.80). In multivariable logistic regression analysis, NEMMI score was significantly and independently associated with MMI (OR: 1.33, 95%CI: 1.13–1.56,p&lt; 0.001), adjusted for recanalization status.Conclusion:The NEMMI score is a quick and simple rating tool of early ischemic changes on CT and could serve as an important surrogate marker for developing malignant edema. Its diagnostic accuracy was similar to CTP and clinical parameters.
EPOS: EEG Processing Open-Source Scripts
Authors: Rodrigues Johannes , Weiß Martin , Hewig Johannes , Allen John J. B. 
Published: June 2021

BackgroundSince the replication crisis, standardization has become even more important in psychological science and neuroscience. As a result, many methods are being reconsidered, and researchers’ degrees of freedom in these methods are being discussed as a potential source of inconsistencies across studies.New MethodWith the aim of addressing these subjectivity issues, we have been working on a tutorial-like EEG (pre-)processing pipeline to achieve an automated method based on the semi-automated analysis proposed by Delorme and Makeig.ResultsTwo scripts are presented and explained step-by-step to perform basic, informed ERP and frequency-domain analyses, including data export to statistical programs and visual representations of the data. The open-source software EEGlab in MATLAB is used as the data handling platform, but scripts based on code provided by Mike Cohen (2014) are also included.Comparison with existing methodsThis accompanying tutorial-like article explains and shows how the processing of our automated pipeline affects the data and addresses, especially beginners in EEG-analysis, as other (pre)-processing chains are mostly targeting rather informed users in specialized areas or only parts of a complete procedure. In this context, we compared our pipeline with a selection of existing approaches.ConclusionThe need for standardization and replication is evident, yet it is equally important to control the plausibility of the suggested solution by data exploration. Here, we provide the community with a tool to enhance the understanding and capability of EEG-analysis. We aim to contribute to comprehensive and reliable analyses for neuro-scientific research.
Is Peripheral Motion Detection Affected by Myopia?
Authors: Wei Junhan , Kong Deying , Yu Xi , Wei Lili , Xiong Yue , Yang Adeline , Drobe Björn , Bao Jinhua , Zhou Jiawei , Gao Yi , He Zhifen 
Published: June 2021

PurposeThe current study was to investigate whether myopia affected peripheral motion detection and whether the potential effect interacted with spatial frequency, motion speed, or eccentricity.MethodsSeventeen young adults aged 22–26 years participated in the study. They were six low to medium myopes [spherical equivalent refractions −1.0 to −5.0 D (diopter)], five high myopes (&lt;-5.5 D) and six emmetropes (+0.5 to −0.5 D). All myopes were corrected by self-prepared, habitual soft contact lenses. A four-alternative forced-choice task in which the subject was to determine the location of the phase-shifting Gabor from the four quadrants (superior, inferior, nasal, and temporal) of the visual field, was employed. The experiment was blocked by eccentricity (20° and 27°), spatial frequency (0.6, 1.2, 2.4, and 4.0 cycles per degree (c/d) for 20° eccentricity, and 0.6, 1.2, 2.0, and 3.2 c/d for 27° eccentricity), as well as the motion speed [2 and 6 degree per second (d/s)].ResultsMixed-model analysis of variances showed no significant difference in the thresholds of peripheral motion detection between three refractive groups at either 20° (F[2,14] = 0.145, p = 0.866) or 27° (F[2,14] = 0.475, p = 0.632). At 20°, lower motion detection thresholds were associated with higher myopia (p &lt; 0.05) mostly for low spatial frequency and high-speed targets in the nasal and superior quadrants, and for high spatial frequency and high-speed targets in the temporal quadrant in myopic viewers. Whereas at 27°, no significant correlation was found between the spherical equivalent and the peripheral motion detection threshold under all conditions (all p &gt; 0.1). Spatial frequency, speed, and quadrant of the visual field all showed significant effect on the peripheral motion detection threshold.ConclusionThere was no significant difference between the three refractive groups in peripheral motion detection. However, lower motion detection thresholds were associated with higher myopia, mostly for low spatial frequency targets, at 20° in myopic viewers.
Are Nutritional Guidelines Followed in the Pediatric Intensive Care Unit?
Authors: Jouancastay Mylène , Guillot Camille , Machuron François , Duhamel Alain , Baudelet Jean-Benoit , Leteurtre Stéphane , Recher Morgan 
Published: June 2021

Background: French (2014) and American (2017) pediatric guidelines recommend starting enteral nutrition (EN) early in pediatric intensive care. The aims of this study were to compare the applicability of the guidelines in the pediatric intensive care unit (PICU) and to identify risk factors of non-application of the guidelines.Methods: This retrospective, single-center study was conducted in a medical–surgical PICU between 2014 and 2016. All patients from 1 month to 18 years old with a length of stay &gt;48 h and an exclusive EN at least 1 day during the PICU stay were included. The outcome variable was application of the 2014 and 2017 guidelines, defined by energy intakes ≥90% of the recommended intake at least 1 day as defined by both guidelines. The risk factors of non-application were studied comparing “optimal EN” vs. “non-optimal EN” groups for both guidelines.Results: In total, 416 children were included (mortality rate, 8%). Malnutrition occurred in 36% of cases. The mean energy intake was 34 ± 30.3 kcal kg−1 day−1. The 2014 and 2017 guidelines were applied in 183 (44%) and 296 (71%) patients, respectively (p &lt; 0.05). Following the 2017 guidelines, enteral energy intakes were considered as “satisfactory enteral intake” for 335 patients (81%). Hemodynamic failure was a risk factor of the non-application of both guidelines.Conclusion: In our PICU, the received energy intake approached the level of intake recommended by the American 2017 guidelines, which used the predictive Schofield equations and seem more useful and applicable than the higher recommendations of the 2014 guidelines. Multicenter studies to validate the pediatric guidelines seem necessary.
Bovine Lactoferrin in the Prevention of Antibiotic-Associated Diarrhea in Children: A Randomized Clinical Trial
Authors: Wronowski Michal F. , Kotowska Maria , Banasiuk Marcin , Kotowski Artur , Kuzmicka Weronika , Albrecht Piotr 
Published: June 2021

Introduction:Antibiotic-associated diarrhea (AAD) is a common adverse reaction to antibiotic treatment affecting up to 21% of children. The aim of the study is to evaluate whether bovine lactoferrin (bLf) might be used for AAD prevention.Materials and Methods:In this prospective, randomized, double-blind, placebo-controlled, single-center study, we enrolled 156 children aged between 1 and 18 years, treated with antibiotic due to acute respiratory or urinary tract infection. We randomly allocated children 1:1 to receive 100 mg of bLf or a placebo twice a day orally for the whole period of antibiotic therapy. The primary outcome was the occurrence of antibiotic-associated diarrhea during and up to 2 weeks after antibiotic therapy. The secondary endpoint was intravenous rehydration or antibiotic withdrawal due to diarrhea. We performed intention-to-treat analysis.Results:We included 150 patients in intention-to-treat analysis. AAD occurred in 16 of 75 (21.3%) patients in bLf group and in 7 of 75 (9.3%) individuals in placebo group [OR = 2.6, (95% CI: 1.01–6.84),p= 0.04]. Relative risk was 2.29 (95% CI: 0.89–5.88). The need for intravenous rehydration occurred in one patient in the placebo group (p= 0.3). We observed no adverse effects in neither of the groups.Discussion:The trial indicated that bLf is not effective in AAD prevention. The risk for AAD was higher in bovine lactoferrin group as compared with placebo. We registered the study protocol onClinicalTrials.gov(NCT02626104).
Design of a Proteolytically Stable Sodium-Calcium Exchanger 1 Activator Peptide for In Vivo Studies
Authors: Wanichawan Pimthanya , Skogestad Jonas , Lunde Marianne , Støle Thea Parsberg , Stensland Maria , Nyman Tuula A. , Sjaastad Ivar , Sejersted Ole M. , Aronsen Jan Magnus , Carlson Cathrine Rein 
Published: June 2021

The cardiac sodium–calcium exchanger (NCX1) is important for normal Na+- and Ca2+-homeostasis and cardiomyocyte relaxation and contraction. It has been suggested that NCX1 activity is reduced by phosphorylated phospholemman (pSer68-PLM); however its direct interaction with PLM is debated. Disruption of the potentially inhibitory pSer68-PLM-NCX1 interaction might be a therapeutic strategy to increase NCX1 activity in cardiac disease. In the present study, we aimed to analyze the binding affinities and kinetics of the PLM-NCX1 and pSer68-PLM-NCX1 interactions by surface plasmon resonance (SPR) and to develop a proteolytically stable NCX1 activator peptide for future in vivo studies. The cytoplasmic parts of PLM (PLMcyt) and pSer68-PLM (pSer68-PLMcyt) were found to bind strongly to the intracellular loop of NCX1 (NCX1cyt) with similar KD values of 4.1 ± 1.0 nM and 4.3 ± 1.9 nM, but the PLMcyt-NCX1cyt interaction showed higher on/off rates. To develop a proteolytically stable NCX1 activator, we took advantage of a previously designed, high-affinity PLM binding peptide (OPT) that was derived from the PLM binding region in NCX1 and that reverses the inhibitory PLM (S68D)-NCX1 interaction in HEK293. We performed N- and C-terminal truncations of OPT and identified PYKEIEQLIELANYQV as the minimum sequence required for pSer68-PLM binding. To increase peptide stability in human serum, we replaced the proline with an N-methyl-proline (NOPT) after identification of N-terminus as substitution tolerant by two-dimensional peptide array analysis. Mass spectrometry analysis revealed that the half-life of NOPT was increased 17-fold from that of OPT. NOPT pulled down endogenous PLM from rat left ventricle lysate and exhibited direct pSer68-PLM binding in an ELISA-based assay and bound to pSer68-PLMcyt with a KD of 129 nM. Excess NOPT also reduced the PLMcyt-NCX1cyt interaction in an ELISA-based competition assay, but in line with that NCX1 and PLM form oligomers, NOPT was not able to outcompete the physical interaction between endogenous full length proteins. Importantly, cell-permeable NOPT-TAT increased NCX1 activity in cardiomyocytes isolated from both SHAM-operated and aorta banded heart failure (HF) mice, indicating that NOPT disrupted the inhibitory pSer68-PLM-NCX1 interaction. In conclusion, we have developed a proteolytically stable NCX1-derived PLM binding peptide that upregulates NCX1 activity in SHAM and HF cardiomyocytes.
Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors
Authors: Wen Yang , Lin Anqi , Zhu Weiliang , Wei Ting , Luo Peng , Guo Linlang , Zhang Jian 
Published: June 2021

Background: Lung cancer has always been the most prevalent cancer. Lung adenocarcinoma (LUAD) is the most common lung cancer subtype and has a high tumor mutation rate. In addition to KRAS, EGFR, ALK, HER2, ROS1, and BRAF, which are known to have high mutation rates, we discovered some new mutated genes, such as catenin alpha-2 (CTNNA2), in LUAD patients treated with immune checkpoint inhibitors (ICIs). These mutant genes are potential therapeutic targets for LUAD.Methods: We analyzed a cohort of LUAD patients with somatic mutation and survival data in the Cancer Genome Atlas (TCGA) database and a cohort of LUAD patients receiving immune checkpoint inhibitors with clinical data and whole-exome sequencing (WES) mutation data to evaluate the role of CTNNA2 gene mutation in LUAD. In addition, CIBERSORT was used to analyze the immune characteristics of CTNNA2 wild-type patients and CTNNA2 mutant-type patients, and gene set enrichment analysis (GSEA) was employed for pathway enrichment analysis. The results were verified by downloading data regarding the drug sensitivity of LUAD cell lines from the Genomics of Drug Sensitivity in Cancer (GDSC) database.Results: We found that CTNNA2 mutation was associated with longer overall survival (OS) in LUAD patients. Analysis of the cohort from the Cancer Genome Atlas showed that patients with CTNNA2 mutation had more tumor neoantigens and a greater tumor mutation burden (TMB). Through further analysis of the tumor immune microenvironment, we found that in LUAD patients with CTNNA2 mutations, the gene expression levels of chemokine C-X-C motif chemokine 9 (CXCL9) and granzyme B (GZMB) were elevated, and the gene expression level of inhibitory receptor killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) was significantly reduced. These alterations might affect gene expression in macrophages, NK cells, and mast cell markers. In addition, LUAD patients with CTNNA2 mutation had a significantly increased number of mutations in DNA damage response (DDR) genes. The drug susceptibility results and gene set enrichment analysis showed that after CTNNA2 mutation occurred, changes were found in the DNA damage response pathway, the phosphoinositide 3-kinase (PI3K) pathway and others, indicating that CTNNA2 mutation can regulate the activation of PI3K and DDR pathways.Conclusion: Our findings provide novel insights into the underlying pathogenesis of LUAD. CTNNA2 mutation can change the immune microenvironment, thereby improving patient prognosis. The results also suggest that CTNNA2 may become a new biomarker and therapeutic target for LUAD in the future.
Physical Activity and Inhibition of ACE Additively Modulate ACE/ACE-2 Balance in Heart Failure in Mice
Authors: Tyrankiewicz Urszula , Olkowicz Mariola , Berkowicz Piotr , Jablonska Magdalena , Smolenski Ryszard T. , Zoladz Jerzy A. , Chlopicki Stefan 
Published: June 2021

Angiotensin-converting enzyme inhibition (ACE-I) and physical activity favorably modulate the ACE/ACE-2 balance. However, it is not clear whether physical activity and ACE-I could synergistically modulate ACE/ACE-2 balance in the course of heart failure (HF). Here, we studied the effects of combined spontaneous physical activity and ACE-I–based treatment on angiotensin (Ang) pattern and cardiac function in a mouse model of HF (Tgαq*44). Tgαq*44 mice with advanced HF (at the age of 12 months) were running spontaneously in a running wheel (exercise training group, ExT) and/or were treated with ACE inhibitor (ACE-I, perindopril, 10 mg/kg) for 2 months. Angiotensin profile was characterized by an LC-MS/MS-based method. The cardiac performance was assessed in vivo by MRI. Ang-(1–7)/Ang II ratio in both plasma and the aorta was significantly higher in the combined treatment group than the ACE-I group or ExT alone, suggesting the additive favorable effects on ACE-2/Ang-(1–7) and ACE/Ang II axes’ balance induced by a combination of ACE-I with ExT. The basal cardiac performance did not differ among the experimental groups of Tgαq*44 mice. We demonstrated additive changes in ACE/ACE-2 balance in both plasma and the aorta by spontaneous physical activity and ACE-I treatment in Tgαq*44 mice. However, these changes did not result in an improvement of failing heart function most likely because the disease was at the end-stage. Ang-(1–7)/Ang II balance represents a valuable biochemical end point for monitoring therapeutic intervention outcome in heart failure.