bluuebunny/crossref_metadata_2025_split huggingface dataset:
FreeSurfer and 3D Slicer-Assisted SEEG Implantation for Drug-Resistant Epilepsy
Authors: Liu Qiangqiang , Wang Junjie , Wang Changquan , Wei Fang , Zhang Chencheng , Wei Hongjiang , Ye Xiaolai , Xu Jiwen 
Published: February 2022

ObjectiveOur study aimed to develop an approach to improve the speed and resolution of cerebral-hemisphere and lesion modeling and evaluate the advantages and disadvantages of robot-assisted surgical planning software.MethodsWe applied both conventional robot planning software (method 1) and open-source auxiliary software (FreeSurfer and 3D Slicer; method 2) to model the brain and lesions in 19 patients with drug-resistant epilepsy. The patients' mean age at implantation was 21.4 years (range, 6–52 years). Each patient received an average of 12 electrodes (range, 9–16) between May and November 2021. The electrode-implantation plan was designed based on the models established using the two methods. We statistically analyzed and compared the duration of designing the models and planning the implantation using these two methods and performed the surgeries with the implantation plan designed using the auxiliary software.ResultsA significantly longer time was needed to reconstruct a cerebral-hemisphere model using method 1 (mean, 206 s) than using method 2 (mean, 20 s) (p &lt; 0.05). Both methods identified a mean of 1.4 lesions (range, 1–5) in each patient. Overall, using method 1 required longer (mean, 130 s; range, 48–436) than using method 2 (mean, 68.1 s; range, 50–104; p &lt; 0.05). In addition, the clarity of the model based on method 1 was lower than that based on method 2. To devise an electrode-implantation plan, it took 9.1–25.5 min (mean, 16) and 6.6–14.8 min (mean, 10.2) based on methods 1 and 2, respectively (p &lt; 0.05). The average target point error of 231 electrodes amounted to 1.90 mm ± 0.37 mm (range, 0.33–3.61 mm). The average entry point error was 0.89 ± 0.26 mm (range, 0.17–1.67 mm). None of the patients presented with intracranial hemorrhage or infection, and no other serious complications were observed.ConclusionsFreeSurfer and 3D Slicer-assisted SEEG implantation is an excellent approach to enhance modeling speed and resolution, shorten the electrode-implantation planning time, and boost the efficiency of clinical work. These well-known, trusted open-source programs do not have explicitly restricted licenses. These tools, therefore, seem well suited for clinical-research applications under the premise of approval by an ethics committee, informed consent of the patient, and clinical judgment of the surgeon.
Altered Microstructural Changes Detected by Diffusion Kurtosis Imaging in Patients With Cognitive Impairment After Acute Cerebral Infarction
Authors: Fan Liting , Ibrahim Fatima Elzahra E. M. , Chu Xiaoqi , Fu Yu , Yan Hongting , Wu Zheng , Tao Chunmei , Chen Xuejing , Ma Yue , Guo Yunchu , Dong Yang , Yang Chao , Ge Yusong 
Published: February 2022

ObjectiveTo detect the microstructural changes in patients with cognitive impairment after acute cerebral infarction using diffusion kurtosis imaging (DKI).Materials and MethodsA total of 70 patients with acute cerebral infarction were divided into two groups: 35 patients with cognitive impairment (VCI group), and 35 patients without cognitive impairment (N-VCI group), according to mini-mental state examination (MMSE) score. Healthy individuals (n = 36) were selected as the normal control (NORM) group. DKI parameters from 28 different brain regions of interest (ROIs) were selected, measured, and compared.ResultsVCI group patients had significantly higher mean diffusion (MD) and significantly lower mean kurtosis (MK) values in most ROIs than those in the N-VCI and NORM groups. DKI parameters in some ROIs correlated significantly with MMSE score. The splenium of corpus callosum MD was most correlated with MMSE score, the correlation coefficient was −0.652, and this parameter had good ability to distinguish patients with VCI from healthy controls; at the optimal cut-off MD value (0.9915), sensitivity was 91.4%, specificity 100%, and the area under the curve value 0.964.ConclusionsPathological changes in some brain regions may underlie cognitive impairment after acute cerebral infarction, especially the splenium of corpus callosum. These preliminary results suggest that, in patients with VCI, DKI may be useful for assessing microstructural tissue damage.
A Modified Dura Puncture Procedure to Reduce Brain Shift in Deep Brain Stimulation Surgery: One Institution's Experience
Authors: Wu Yu-Xi , Xiang Wei , Wang Jia-Jing , Liu Xiao-Ming , Yi Dong-Ye , Tian Han , Zhao Hong-Yang , Jiang Xiao-Bing , Fu Peng 
Published: February 2022

ObjectiveThe therapeutic effect of deep brain stimulation (DBS) surgery mainly depends on the accuracy of electrode placement and the reduction in brain shift. Among the standard procedures, cerebrospinal fluid (CSF) loss or pneumocephalus caused by dura incision (DI) is thought to be the main reason for brain shift and inaccuracy of electrode placement. In the current study, we described a modified dura puncture (DP) procedure to reduce brain shift and compare it with the general procedure of DBS surgery in terms of electrode placement accuracy.Materials and MethodsWe retrospectively analyzed a series of 132 patients who underwent DBS surgery in Wuhan Union Hospital from December 2015 to April 2021. According to the different surgery procedures, patients were classified into two cohorts: the DI group (DI cohort) had 49 patients who receive the general procedure, and the DP group (DP cohort) had 83 patients who receive the modified procedure. Postoperative pneumocephalus volume (PPV) and CSF loss volume, electrode fusion error (EFE), and trajectory number were calculated. Meanwhile, intraoperative electrophysiological signal length (IESL), electrode implantation duration, and other parameters were analyzed.ResultsIn the current study, we introduced an improved electrode implantation procedure for DBS surgery named the DP procedure. Compared with the general DI cohort (n = 49), the modified DP cohort (n = 83) had a shorter electrode implantation duration (p &lt; 0.0001), smaller PPV, lower CSF leakage volume (p &lt; 0.0001), and smaller EFE (p &lt; 0.0001). There was no significant difference in IESL (p &gt; 0.05) or adverse events (perioperative cerebral haematoma, skin erosion, epilepsy, p &gt; 0.05) between the two cohorts.ConclusionThe DP procedure is a modified procedure that can reduce brain shift and ensure implantation accuracy during DBS surgery without adverse events.
Combined Subthalamic and Nigral Stimulation Modulates Temporal Gait Coordination and Cortical Gait-Network Activity in Parkinson’s Disease
Authors: Wagner Jonas R. , Schaper Miriam , Hamel Wolfgang , Westphal Manfred , Gerloff Christian , Engel Andreas K. , Moll Christian K. E. , Gulberti Alessandro , Pötter-Nerger Monika 
Published: February 2022

BackgroundFreezing of gait (FoG) is a disabling burden for Parkinson’s disease (PD) patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra (STN+SN DBS) moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear.MethodsTwelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in a standardized stepping in place paradigm. Patients executed the task with DBS switched off (STIM OFF), conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes.ResultsClinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta (4–8 Hz), alpha (9–13 Hz), and high-beta (21–30 Hz) band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas.ConclusionsSTN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD.
Efficacy and Safety of Cellular Immunotherapy by Local Infusion for Liver Tumor: A Systematic Review and Meta-Analysis
Authors: Chen Shanshan , Chen Hualei , Zhang Yongchao , Li Wei 
Published: February 2022

BackgroundCellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied.MethodsThe PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0.ResultsThe eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%–70%). The pooled OS rate was 94% (95% CI: 83%–100%) at 6 months, 87% (95% CI: 74%–96%) at 12 months, and 42% (95% CI: 16%–70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%).ConclusionsImmune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.
Circular RNAs are Potential Prognostic Markers of Head and Neck Squamous Cell Carcinoma: Findings of a Meta-Analysis Study
Authors: Nath Moumita , Roy Dibakar , Choudhury Yashmin 
Published: February 2022

BackgroundSeveral studies have reported the role of circRNAs in the pathogenesis, diagnosis and prognosis of different cancers. This meta-analysis study aimed to evaluate the potential of using circRNAs as prognostic biomarkers of head and neck squamous cell carcinoma (HNSCC).Methods816 relevant articles were retrieved from PubMed and Science Direct databases, out of which 17 met the inclusion criteria. These 17 studies were assessed for quality by the Newcastle-Ottawa Scale (NOS) system, and 9 high quality studies (NOS&gt;7) were included in the meta-analysis. Cochran Q test and the I square (I2) metric were calculated to detect potential heterogeneity among studies. Sensitivity analysis was performed to validate the credibility of outcomes, and publication bias was determined using Begg’s funnel plot and Egger’s test. Hazard ratio (HR) and 95% Confidence Intervals (CIs) were used to evaluate overall survival (OS) of HNSCC patients by univariate and multivariate analyses.ResultsThe dysregulated levels of 9 circRNAs (circPVT1, circCORO1C, circ_0000199, circCUX1, circPARD3, circMYC, circ_0102272, circ_0092125 and circ_00072387) were inversely related to OS of HNSCC patients [upregulated circRNA (univariate analysis: HR = 3.40, 95% CI: 2.66-4.36, p &lt; 0.0001, I2 = 0%; multivariate analysis: HR = 3.33, 95% CI: 2.54-4.38, p &lt; 0.0001, I2 = 0%), downregulated circRNA (univariate analysis: HR = 2.83, 95% CI: 1.73-4.65, p &lt; 0.0001, I2 = 57.8%; multivariate analysis: HR = 2.35, 95% CI: 1.42-3.89, p = 0.0009, I2 = 0%)]. The individual HR for these 9 circRNAs indicated inverse relation to OS, validating the overall HR. The dyregulated levels of these circRNAs were also associated with poor clinicopathological outcomes such as primary tumor size, lymph node metastasis, distant metastasis and poor tumor (T), nodes (N), metastases (M); i.e TNM staging, and six of these circRNAs regulated diverse micro RNAs, revealing their role in tumorigenesis and cancer progression.ConclusionNine different circRNAs dysregulated in HNSCC tumors may serve as potential prognostic markers of HNSCC. These markers are associated with reduced OS and poor clinicopathological outcomes of HNSCC patients. They are also involved in the pathogenesis and progression of HNSCC through diverse mechanisms.
Identification of CXCL10 as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma
Authors: Qu Genyi , Wang Hao , Yan Huiqin , Liu Genlin , Wu Min 
Published: February 2022

BackgroundOne of the widespread forms of kidney tumor is clear cell renal cell carcinoma (ccRCC), with poor prognosis and insensitivity to radio chemotherapy as there is limited capacity to understand the disease mechanism. This study aims at identifying potential biomarkers and the underlying processes of ccRCC using bioinformatics analysis.MethodsTranscriptome data of relevant samples were downloaded from The Cancer Genome Atlas (TCGA) database. R software was used to screen differentially expressed genes (DEGs) using the “edgeR” package. Two types of analysis—Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment—were accomplished by applying Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Search Tool for the Retrieval of Interacting Genes database (STRING) online bioinformatics tools. A protein–protein interaction (PPI) network of the identified DEGs was constructed using Cytoscape software, and hub genes were subsequently selected via the Cytohubba plug-in. The selected genes were input into Oncomine for verification. Finally, selected hub genes were analyzed by doing survival analysis to notice the relationship between survival (OS) rate and the selected genes’ level of expression.ResultsThere were 1,855 DEGs found connected to ccRCC, with 1,207 upregulated genes and 648 downregulated genes. G-protein-coupled receptor signaling pathway, integral component of membrane, calcium ion binding, and cytokine–cytokine receptor interaction were among the DEGs discovered. Oncomine confirmed the top six hub genes from the PPI network (C3, CXCR3, CXCL10, CCR5, CCL4, and CCL5). A high level of expression of CXCL10, one of these hub genes, was linked to a poor prognosis in individuals with ccRCC. The results of survival analysis showed that the expression level of CXCL10 was significantly correlated with the prognosis of ccRCC patients (p &lt; 0.05).ConclusionsFrom the analysis, the following results were drawn: CXCL10 might be a potential prognostic biomarker and novel therapeutic target for ccRCC.
The Pharmacological and Structural Basis of the AahII–NaV1.5 Interaction and Modulation by the Anti-AahII Nb10 Nanobody
Authors: Hmaidi Riadh , Ksouri Ayoub , Benabderrazek Rahma , Antonietti Viviane , Sonnet Pascal , Gautier Mathieu , Bouhaouala-Zahar Balkiss , Ouadid-Ahidouch Halima 
Published: February 2022

Scorpion α-toxins are neurotoxins that target the fast inactivation mechanism of voltage-gated sodium (NaV) channels leading to several neuro- and cardiotoxic effects in mammals. The toxin AahII is the most active α-toxin from the North African scorpionAndroctonus australis Hectorthat slows the fast inactivation of NaVchannels. To fight scorpion envenomation, an anti-AahII nanobody named NbAahII10 (Nb10) was developed. The efficiency of this nanobody has been evaluatedin vivoon mice, but its mechanism of action at the cellular level remains unknown. Here we have shown that AahII toxin slows the fast inactivation of the adult cardiac NaV1.5 channels, expressed in HEK293 cells, in a dose-dependent manner, while current amplitude was not affected. The inactivation of NaV1.5 is slower by a factor of 4, 7, and 35 in the presence of [AahII] at 75, 150, and 300 nM, respectively. The washout partially reversed the toxin effect on inactivation from 8.3 ± 0.9 ms to 5.2 ± 1.2 ms at 75 nM. We have also demonstrated that the highly neutralizing Nb10 can fully reverse the effect of AahII toxin on the channel inactivation kinetics even at the 1:1 M ratio. However, the 1:0.5 M ratio is not able to neutralize completely the AahII effect. Therefore, the application of Nb10 promotes a partial abolishment of AahII action. Bioinformatic analysis and prediction of NaV1.5-driven docking with AahII show that Ala39 and Arg62 of AahII play a crucial role to establish a stable interaction through H-bound interactions with Gln1615 and Lys1616 (S3–S4 extracellular loop) and Asp1553 (S1–S2 loop) from the voltage-sensing domain IV (VSD4) of NaV1.5, respectively. From this, we notice that AahII shares the same contact surface with Nb10. This strongly suggests that Nb10 dynamically replaces AahII toxin from its binding site on the NaV1.5 channel. At the physiopathological level, Nb10 completely neutralized the enhancement of breast cancer cell invasion induced by AahII. In summary, for the first time, we made an electrophysiological and structural characterization of the neutralization potent of Nb10 against the α-scorpion toxin AahII in a cellular model overexpressing NaV1.5 channels.
Palatability Assessment of Carbocysteine Oral Solution Strawberry Taste Versus Carbocysteine Oral Solution Mint Taste: A Blinded Randomized Study
Authors: Peng Yaguang , Zhang Huan , Gao Liucun , Wang Xiaoling , Peng Xiaoxia 
Published: February 2022

Objective: To compare and evaluate the palatability of two carbocysteine oral solutions (strawberry vs. mint taste) among healthy children aged 2–12 years.Methods: A randomized, triple-blind, crossover, palatability trial in 42 children aged 2–12 years. All subjects received two preparations of carbocysteine oral solutions (strawberry vs. mint) according to randomized administration sequences, and the administration process was recorded by video. The palatability assessed by emotional valences was performed using a facial action coding system by FaceReader™, which reflected the quantification degree of emotion; a positive value represents positive emotion, and a negative value represents negative emotion. At the same time, a face-to-face interview was conducted for 5- to 12-year-old participants. Then, the taste preferential rates were compared to assess the palatability of two carbocysteine oral solutions.Results: Forty-two children were enrolled in this study. Twenty children first tasted the carbocysteine oral solution mint taste and then the strawberry taste preparation (M-S sequence), while 22 children tasted the strawberry preparation first and then the mint one (S-M sequence). The emotional valence of mint preparation (−0.9 in M-S and −1.2 in S-M) was both relatively lower than that of strawberry taste (both −0.7 in M-S and S-M) in two sequences; 69.0% (29/42) of participants’ emotional valences for strawberry preparation were higher than those for mint preparation. Among 27 participants aged ≥5 years, the taste preference rate was 88.5% (23/26) for the strawberry preparation (one missing value for the taste preference), and 77.8% of participants (21/27) chose the strawberry preparation if they had to take the medicine one more time.Conclusion: The carbocysteine oral solution with strawberry taste is an appealing preparation since it was better received by children. The facial action coding system could be an effective alternative for palatability assessment of pediatric pharmaceutical products.
Relationships Between Maximal Aerobic Speed, Lactate Threshold, and Double Poling Velocity at Lactate Threshold in Cross-Country Skiers
Authors: Johansen Jan-Michael , Sunde Arnstein , Helgerud Jan , Støren Øyvind 
Published: February 2022

PurposeTo investigate the relationships between maximal aerobic speed (MAS), lactate threshold in per cent of peak oxygen uptake (LT) and velocity at LT (LTv) in cross-country skiers. Secondly, we aimed to explore the fit of an equation previously used in cyclists and runners in a cohort of well-trained, competitive cross-country skiers for calculation of LTv. Thirdly, we aimed to investigate if a new LTv could still be calculated after a period of regular training only by providing a new MAS.MethodsNinety-five competitive cross-country skiers (65 males and 30 females) were tested for maximal oxygen uptake (VO2max), peak oxygen uptake in double poling (DP-VO2peak), oxygen cost of double poling (CDP), LT, and LTv. Thirty-five skiers volunteered to be tested 3 months later to evaluate potential changes in LT and LTv.ResultsVelocity at LT was mainly determined by MAS (r = 0.88, p &lt; 0.01). LT did not show a significant impact on LTv. The product of MAS·LT precisely predicted LTv at baseline (r = 0.99, SEE = 2.4%), and by only measuring MAS, a new LTv could be accurately calculated (r = 0.92, SEE = 6.8%) 3 months later in a sub-set of the initial 95 skiers (n = 35).ConclusionThe results suggest that LT has minor impact on LTv in DP tested in a laboratory. LTv seemed to be predominantly determined by MAS, and we suggest to put more focus on MAS and less on LT and LTv in regular testing to evaluate aerobic performance capacity in DP.
Sweet Immunity Aspects during Levan Oligosaccharide-Mediated Priming in Rocket against Botrytis cinerea
Authors: Versluys Maxime , Van den Ende Wim 
Published: February 2022

New strategies are required for crop protection against biotic stress. Naturally derived molecules, including carbohydrates such as fructans, can be used in priming or defense stimulation. Rocket (Eruca sativa) is an important leafy vegetable and a good source of antioxidants. Here, we tested the efficacy of fructan-induced immunity in the Botrytis cinerea pathosystem. Different fructan types of plant and microbial origin were considered and changes in sugar dynamics were analyzed. Immune resistance increased significantly after priming with natural and sulfated levan oligosaccharides (LOS). No clear positive effects were observed for fructo-oligosaccharides (FOS), inulin or branched-type fructans. Only sulfated LOS induced a direct ROS burst, typical for elicitors, while LOS behaved as a genuine priming compound. Total leaf sugar levels increased significantly both after LOS priming and subsequent infection. Intriguingly, apoplastic sugar levels temporarily increased after LOS priming but not after infection. We followed LOS and small soluble sugar dynamics in the apoplast as a function of time and found a temporal peak in small soluble sugar levels. Although similar dynamics were also found with inulin-type FOS, increased Glc and FOS levels may benefit B. cinerea. During LOS priming, LOS- and/or Glc-dependent signaling may induce downstream sweet immunity responses.