bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional Word Processing in Patients With Juvenile Myoclonic Epilepsy
Authors: Rainer Lucas Johannes , Kronbichler Martin , Kuchukhidze Giorgi , Trinka Eugen , Langthaler Patrick Benjamin , Kronbichler Lisa , Said-Yuerekli Sarah , Kirschner Margarita , Zimmermann Georg , Höfler Julia , Schmid Elisabeth , Braun Mario 
Published: June 2022

ObjectiveAccording to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME).MethodsWe recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing.ResultsIn support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME.SignificanceThese results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME.
15-Hydroxyprostaglandin Dehydrogenase Is a Predictor of Stroke-Associated Pneumonia
Authors: Xu Yunfei , Qiao Haoduo , Yang Shun , Zhou Lin , Zhao Yao , Xu Qing , Miao Shuying , Yuan Dun , Zhao Jie , Liu Ying 
Published: June 2022

Background and PurposeStroke is a serious fatal and disabling disease. Stroke-associated pneumonia (SAP) is the most common complication of stroke, which may further aggravate the stroke. The prevention and early prediction of SAP is a key clinical strategy. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is involved in pneumonia, while its relationship with SAP has yet to be determined. Therefore, we investigated the predictive value of 15-PGDH for SAP and visualized their relationship.MethodsStroke patients were recruited and divided into SAP group and Non-SAP group. Baseline demographic and clinical data were obtained from the medical record system, blood samples were collected to detect relevant variables and 15-PGDH levels. Patient characteristics were compared with a t-test. Binary logistic regression analysis was performed to determine the predictive value of 15-PGDH for SAP. Restricted cubic splines (RCS) were performed to visualize the relationship between 15-PGDH and SAP risk. Finally, the SAP patient characteristics between the severe group and mild group were compared.Results50 patients were enrolled and divided into SAP group (n = 26) and Non-SAP group (n = 24). 15-PGDH in the SAP group was lower than that in the Non-SAP group (0.258 ± 0.275 vs. 0.784 ± 0.615, p = 0.025). Binary logistic regression analysis revealed that the lower 15-PGDH, the higher the risk of SAP (OR = 0.04, 95%CI, 0.010–0.157, p &lt; 0.001). The RCS model showed the L-shaped relationship between 15-PGDH and SAP.ConclusionsIn stroke patients, serum 15-PGDH is a valuable biomarker for predicting SAP. There is an L-shaped relationship between the level of 15-PGDH and the risk of SAP.
A New Scale for Predicting the Risk of In-hospital Mortality in Patients With Traumatic Spinal Cord Injury
Authors: Gong Yining , Du Jinpeng , Hao Dingjun , He Baorong , Cao Yang , Gao Xiangcheng , Zhang Bo , Yan Liang 
Published: June 2022

PurposeTo analyze the relative factors influencing in-hospital mortality in patients with traumatic spinal cord injury (TSCI), and develop a score scale for predicting the risk of in-hospital mortality.MethodWe reviewed the medical records from 59 spine centers in mainland China from 1 January 2018 to 31 December 2018. The inclusion criteria were (1) confirmed diagnosis of TSCI, (2) hospitalization within 7 days of injury, and (3) affecting neurological level from C1 to L1. The exclusion criteria were (1) readmission, and (2) incomplete data. Included patients were classified into the survival and non-survival groups according to their status at discharge. Univariate and multivariate logistic regressions were performed to identify the factors related to in-hospital mortality in patients with TSCI. A new scale was developed, and the mortality rate in each risk group was calculated.ResultsOf the 3,176 participants, 23 (0.7%) died in the hospital, and most of them died from respiratory diseases (17/23, 73.9%). After univariate and multivariate logistic regression analysis, cervical spinal cord injury [odds ratio (OR) = 0.264, 95% confidence interval (CI): 0.076–0.917, P = 0.036], abdominal visceral injury (OR = 3.778, 95% CI: 1.038–13.755, P = 0.044), the American Spinal Injury Association (ASIA) score on admission (A: reference; B:OR = 0.326, 95% CI: 0.093–1.146, P = 0.081; C:OR = 0.070, 95% CI: 0.016–0.308, P &lt; 0.001; D:OR = 0.069, 95% CI: 0.019–0.246, P &lt; 0.001), and surgery (OR = 0.341, 95% CI: 0.146–0.796, P = 0.013) were significantly associated with in-hospital mortality. Scores for each of the four factors were derived according to mortality rates. The sum of the scores from all four factors was included in the scoring system and represented the risk of in-hospital mortality. The in-hospital mortality risk of the low-risk (0–3 points), moderate-risk (4–5 points), and high-risk groups (6–8 points) was 0.3, 2.7, and 9.7%, respectively (P &lt; 0.001).ConclusionsCervical spinal cord injury, abdominal visceral injury, ASIA score on admission, and surgery were significantly associated with in-hospital mortality in patients with TSCI and stable condition. The scale system may be beneficial for clinical decision-making and for communicating relevant information to patients and their families.
Current Steering Using Multiple Independent Current Control Deep Brain Stimulation Technology Results in Distinct Neurophysiological Responses in Parkinson’s Disease Patients
Authors: Peeters Jana , Boogers Alexandra , Van Bogaert Tine , Gransier Robin , Wouters Jan , Nuttin Bart , Mc Laughlin Myles 
Published: June 2022

BackgroundDeep brain stimulation (DBS) is an effective neuromodulation therapy to treat people with medication-refractory Parkinson’s disease (PD). However, the neural networks affected by DBS are not yet fully understood. Recent studies show that stimulating on different DBS-contacts using a single current source results in distinct EEG-based evoked potentials (EPs), with a peak at 3 ms (P3) associated with dorsolateral subthalamic nucleus stimulation and a peak at 10 ms associated with substantia nigra stimulation. Multiple independent current control (MICC) technology allows the center of the electric field to be moved in between two adjacent DBS-contacts, offering a potential advantage in spatial precision.ObjectiveDetermine if MICC precision targeting results in distinct neurophysiological responses recorded via EEG.Materials and MethodsWe recorded cortical EPs in five hemispheres (four PD patients) using EEG whilst employing MICC to move the electric field from the most dorsal DBS-contact to the most ventral in 15 incremental steps.ResultsThe center of the electric field location had a significant effect on both the P3 and P10 amplitude in all hemispheres where a peak was detected (P3, detected in 4 of 5 hemispheres, p &lt; 0.0001; P10, detected in 5 of 5 hemispheres, p &lt; 0.0001). Post hoc analysis indicated furthermore that MICC technology can significantly refine the resolution of steering.ConclusionUsing MICC to incrementally move the center of the electric field to locations between adjacent DBS-contacts resulted in significantly different neurophysiological responses that may allow further precision of the programming of individual patients.
Changes in Adiposity and Cerebrospinal Fluid Biomarkers Following a Modified Mediterranean Ketogenic Diet in Older Adults at Risk for Alzheimer’s Disease
Authors: Brinkley Tina E. , Leng Iris , Register Thomas C. , Neth Bryan J. , Zetterberg Henrik , Blennow Kaj , Craft Suzanne 
Published: June 2022

BackgroundKetogenic diets have been used to treat both obesity and neurological disorders, including epilepsy and more recently Alzheimer’s disease (AD), likely due to favorable effects on both central and peripheral metabolism. Improvements in body composition have also been reported; however, it is unclear if diet-induced changes in adiposity are related to improvements in AD and related neuropathology.PurposeWe examined the effects of a Modified Mediterranean Ketogenic (MMK) diet vs. an American Heart Association (AHA) diet on body weight, body composition, and body fat distribution and their association with cerebrospinal fluid (CSF) biomarkers in older adults at risk for AD.MethodsTwenty adults (mean age: 64.3 ± 6.3 years, 35% Black, 75% female) were randomly assigned to a crossover trial starting with either the MMK or AHA diet for 6 weeks, followed by a 6-week washout and then the opposite diet for 6 weeks. At baseline and after each diet adiposity was assessed by dual-energy x-ray absorptiometry and CSF biomarkers were measured. Linear mixed effect models were used to examine the effect of diet on adiposity. Spearman correlations were examined to assess associations between adiposity and CSF biomarkers.ResultsAt baseline there was a high prevalence of overweight/obesity and central adiposity, and higher visceral fat and lower peripheral fat were associated with an adverse CSF biomarker profile. The MMK and AHA diets led to similar improvements in body composition and body fat distribution. Significant correlations were found between changes in adiposity and changes in CSF biomarkers (r’s = 0.63–0.92, p’s &lt; 0.05), with notable differences by diet. Decreases in body fat on the MMK diet were related to changes in Aβ biomarkers, whereas decreases in body fat on the AHA diet were related to changes in tau biomarkers and cholinesterase activity. Interestingly, increases in CSF Aβ on the MMK diet occurred in those with less fat loss.ConclusionAn MMK diet leads to favorable changes in body composition, body fat distribution, and CSF biomarkers. Our data suggest that modest weight loss that maximizes visceral fat loss and preserves peripheral fat, may have the greatest impact on brain health.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02984540].
Tumor Budding as a Marker for Poor Prognosis and Epithelial–Mesenchymal Transition in Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Thakur Nishant , Ailia Muhammad Joan , Chong Yosep , Shin Ok Ran , Yim Kwangil 
Published: June 2022

IntroductionCurrently, tumor budding (TB) is considered to predict the prognosis of patients. The prognostic significance of TB has also been explored in patients with lung cancer, but has not been fully clarified. In the present meta-analysis, we evaluated the prognostic significance, clinicopathological value, and relationship with epithelial–mesenchymal transition (EMT) of TB in lung cancer.MethodsThe MEDLINE, EMBASE, and Cochrane databases were searched up to July 7, 2021, for the relevant articles that showed the relationship between TB and prognosis in patients with lung cancer. For statistical analysis, we used pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) to assess the correlation between high-grade TB expression and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), clinicopathological factors, and EMT markers.ResultsA total of 3,784 patients from 10 independent studies were included in the statistical analysis. Our results indicated that high-grade TB was significantly associated with poor OS [HR 1.64 (95% CI, 1.43–1.87)] and DFS [HR 1.65 (95% CI, 1.22–2.25)]. In terms of clinicopathological characteristics, high-grade TB was associated with larger tumor size, higher T and N stage, pleural invasion, vascular invasion, lymphatic invasion, and severe nuclear atypia. Interestingly, smoking showed significant association with high-grade TB, despite the fact that previous studies could not show a significant relationship between them. Furthermore, through our systematic analysis, high-grade TB showed a significant relationship with EMT markers.ConclusionOur findings indicate that high-grade TB is associated with a worse prognosis in patients with lung cancer. TB evaluation should be implemented in routine pathological diagnosis, which may guide the patient’s treatment.
A Novel and Easy-to-Promote Prognostic Model for Patients With Uveal Melanoma
Authors: Yue Han , Xu Binbin , Gao Jian , Bi Yingwen , Xue Kang , Guo Jie , Zhang Rui , Ren Hui , Yuan Yifei , Qian Jiang 
Published: June 2022

PurposeTo establish an easy and widely applicable prognostic prediction model for uveal melanoma (UM) based on a Chinese population.Patients and MethodsA total of 295 consecutive cases treated at the Eye &amp; ENT Hospital of Fudan University were included as the primary cohort, and 256 cases were included in the validation cohorts from two external Caucasian databases. Clinicopathological data were collected retrospectively, and nomogram models were formulated based on multivariable analysis. The concordance index (C-index), AUC (area under the Receiver Operating Characteristic, ROC curve), and Brier score were calculated and compared.ResultsBased on the training cohort, a nomogram model was established with five relevant variables: age, tumor size, ciliary body involvement, non-spindle cell type and extra-scleral extension. The C-index was 0.737, the 3- and 5-year AUCs were 0.767 and 0.742, and the Brier scores for 3- and 5-year survival were 0.082 and 0.129, respectively, which showed superior prediction compared to that of the Tumor, Node and Metastasis staging system. The model also displayed good discrimination and calibration in the external validation cohorts. By risk stratification, patients could be divided into low- and high-risk groups, and the overall survival curves displayed significant differences in the training and validation cohorts.ConclusionOur nomogram model was simple and accurate at predicting the overall survival of patients with UM. It was established based on Asian patients and proved suitable for Caucasian patients; thus, it has a wide range of potential applications, especially for patients living in less medically developed countries and regions.
Combination of Radiofrequency Ablation With Resiquimod to Treat Hepatocellular Carcinoma Via Inflammation of Tumor Immune Microenvironment and Suppression of Angiogenesis
Authors: Tian Zhou , Hong Baojian , Chen Jianzhong , Tang Zhe 
Published: June 2022

BackgroundRadiofrequency ablation (RFA) destroys tumors through hyperthermic injury, which induces the release of immunogenic intracellular substrates and damages associated molecular patterns (DAMPs) to evoke a systemic immune response, but its therapeutic effect is limited. This study aimed to combine RFA with an immunomodulator, resiquimod (R848), to enhance the RFA-induced antitumor immunity.MethodsWe performed RFA on subcutaneous tumors in immunocompetent mice and intraperitoneally injected R848 to observe the efficacy of the combination therapy. Our research investigated changes in the composition of tumor-infiltrating immune cells in primary and distant tumors by flow cytometry. Natural killer (NK) cell depletion experiment was applied to confirm the role of NK cell in the combination therapy. The expression levels of cytokines and chemokines were detected by real-time quantitative PCR. Immunohistochemical test was conducted to reveal tumor angiogenesis, tumor proliferation, and apoptosis after the different treatments.Results and ConclusionCompared with RFA or R848 monotherapy, the combination therapy significantly slowed the tumor growth, prolonged the survival time, and shrank the tumor-draining lymph nodes of tumor-bearing mice. The flow cytometry results showed that tumor-infiltrating immune cells, total T cells, the ratio of CD8+ T and NK cells to CD45+ cells, and functional NK cells were obviously increased after the combined treatment. Distal tumor growth was also suppressed, and the profile of tumor-infiltrating immune cells was remodeled, too. In addition, the additive effect of the combination therapy disappeared after NK cell depletion. Furthermore, immunohistochemical results verified that R848 inhibited tumor angiogenesis in murine liver cancer, and the combination therapy promoted tumor cell apoptosis. In conclusion, our data suggest that RFA combined with R848 stimulated a stronger antitumor immune response and effectively inhibited liver cancer progression in a NK cell-dependent manner. Meanwhile, we confirmed that R848 inhibited tumor angiogenesis and promoted apoptosis in murine liver cancer. Overall, this is a promising therapeutic strategy to improve the efficacy of RFA in the treatment of liver cancer and provides a novel option for combined thermal ablation and immunotherapy.
The Identification of Necroptosis-Related Subtypes, the Construction of a Prognostic Model, and the Characterization of the Tumor Microenvironment in Gliomas
Authors: Ba Yueyang , Su Jiahao , Gao Shuangqi , Liao Zhi , Wu Zhimin , Cao Chengan , Liang Chaofeng , Gong Jin , Guo Ying 
Published: June 2022

Necroptosis is a recently discovered form of cell death that plays a vital role in the progression of cancer, the spread of metastases, and the immunologic response to tumors. Due to the dual role of necrotic apoptotic processes in tumor pathogenesis and the heterogeneity of gliomas, the function of necroptosis in the glioma microenvironment is still poorly understood. We characterized the expression of necroptosis-related genes (NRGs) within glioma samples at both the genetic and transcriptional levels, identifying three distinct subtypes. Additionally, we constructed a risk score, which is capable of accurately predicting patient prognosis, correlates with tumor mutation burden (TMB), tumor stem cell index (CSC), immune checkpoints, and predicts tumor drug sensitivity. To facilitate its application in the clinic, we developed a nomogram and demonstrated that it predicts the prognosis of glioma patients with good accuracy and reliability using multiple datasets. We examined the function of necroptosis in the tumor microenvironment (TME) and the prognosis of gliomas, which may be useful for guiding individualized treatment plans for gliomas targeting necroptosis.
The Effect of Serine Protease Inhibitors on Visceral Pain in Different Rodent Models With an Intestinal Insult
Authors: Ceuleers Hannah , Hanning Nikita , De bruyn Michelle , De Man Joris G , De Schepper Heiko U , Li Qian , Liu Liansheng , Abrams Steven , Smet Annemieke , Joossens Jurgen , Augustyns Koen , De Meester Ingrid , Pasricha Pankaj J , De Winter Benedicte Y 
Published: June 2022

Background: Serine proteases are believed to play a key role in the origin of abdominal pain in IBD and IBS. We previously demonstrated a reduction of visceral pain in a post-inflammatory IBS rat model after a single intraperitoneal or intracolonic administration of a serine protease inhibitor. The aim of this study was to investigate the efficacy of serine protease inhibition on visceral pain in two different animal models involving a colonic insult based either on acute inflammation or on neonatal irritation. Moreover, protease profiling was explored in the acute colitis model.Methods: An acute 2,4,6-trinitrobenzenesulphonic acid (TNBS) colitis rat model and a chronic neonatal acetic acid mouse model were used in this study. Visceral sensitivity was quantified by visceromotor responses (VMRs) to colorectal distension, 30 min after intraperitoneal administration of the serine protease inhibitors nafamostat, UAMC-00050 or their vehicles. Colonic samples from acute colitis rats were used to quantify the mRNA expression of a panel of serine proteases and mast cell tryptase by immunohistochemistry. Finally, proteolytic activities in colonic and fecal samples were characterized using fluorogenic substrates.Key Results: We showed a significant and pressure-dependent increase in visceral hypersensitivity in acute colitis and neonatal acetic acid models. UAMC-00050 and nafamostat significantly reduced VMRs in both animal models. In acute colitis rats, the administration of a serine protease inhibitor did not affect the inflammatory parameters. Protease profiling of these acute colitis animals revealed an increased tryptase immunoreactivity and a downregulation of matriptase at the mRNA level after inflammation. The administration of UAMC-00050 resulted in a decreased elastase-like activity in the colon associated with a significantly increased elastase-like activity in fecal samples of acute colitis animals.Conclusion: In conclusion, our results suggest that serine proteases play an important role in visceral hypersensitivity in an acute TNBS colitis model in rats and a neonatal acetic acid model in mice. Moreover, we hypothesize a potential mechanism of action of UAMC-00050 via the alteration of elastase-like proteolytic activity in acute inflammation. Taken together, we provided fundamental evidence for serine protease inhibitors as a promising new therapeutic strategy for abdominal pain in gastrointestinal diseases.