bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
Authors: Jin Xin , Chen Liwei , Zhou Ning , Ni Hong , Zu Lingling , He Jinling , Yang Lingqi , Zhu Yifan , Sun Xiaoyue , Li Xiaojiang , Xu Song 
Published: December 2021

Background:Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear.Method:The expression levels ofLRMPmRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). LRMP protein expression was examined using the Human Protein Atlas.In vitroexperiments, including qRT-PCR Western blot and immunohistochemistry staining were also performed to investigate LRMP expression. GEPIA2 and Kaplan-Meier plotter databases were used to analyze the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed using gene set enrichment analysis. Moreover, we also constructed plasmids to overexpress LRMP and explored the effect of LRMP in A549 cell line. Additionally, Tumor Immune single-cell Hub was used to investigate the distribution of LRMP in the LUAD immune microenvironment; TIMER and CIBERSORT were used to investigate the relationships amongLRMP,LRMPco-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0.Results:The expression ofLRMPwas significantly lower in LUAD tissues and cell lines. HighLRMPexpression is associated with a better prognosis in patients with LUAD.In vitroexperimental studies demonstrated that overexpression of LRMP could decrease the proliferation, migration and invasion in A549 cells, and downregulated multiple oncogenic signaling pathways, including p-STAT3, p-PI3K-p-AKT, p-MEK and EMT pathways. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. LRMP and its co-expressed genes were positively correlated with various tumor-infiltrating immune cells and their markers. Additionally, LRMP positively correlated with immune checkpoints.Conclusions:Our data suggest that LRMP may act as a tumor suppressor gene and indicates a better prognosis. Moreover, LRMP is associated with immune infiltrates which may be involved in immunotherapy response in LUAD. Further studies are needed to validate these findings.
A Nomogram Model for Predicting the Response to Transcatheter Arterial Embolization in Patients With Symptomatic Hepatic Hemangioma
Authors: Liu Qinqin , You Nan , Zhu Jiangqin , Li Jing , Wu Ke , Wang Zheng , Wang Liang , Zhu Yinan , Gu Huiying , Peng Xuehui , Zheng Lu 
Published: December 2021

Background:Transcatheter arterial embolization (TAE) is regarded as an effective treatment for patients with symptomatic hepatic hemangioma. However, few studies have evaluated the efficacy of TAE alone for treating hepatic hemangioma. The aim of this study was to identify the factors that influence the response to TAE and formulate a quantitative nomogram to optimize the individualized management of hepatic hemangioma.Methods:We retrospectively studied 276 patients treated with TAE for hepatic hemangioma at our center from January 2011 to December 2019. The full cohort was randomly divided into training and validation cohorts. After assessing the potential predictive factors for the efficacy of TAE in the training cohort, a nomogram model was established and evaluated by discrimination and calibration.Results:During follow-up, the symptom relief rate was 100%. The tumor blood supply (p&lt; 0.001), tumor number (p= 0.004), and tumor size (p= 0.006) were identified as significant predictors of the failure of tumor shrinkage in response to TAE. The nomogram model showed favorable discrimination and calibration, with a C-index of 0.775 (95% CI, 0.705–0.845) in the training cohort, which was further confirmed in the validation cohort (C-index 0.768; 95% CI, 0.680–0.856). The side effects of TAE were relatively minor and included mainly abdominal pain, nausea, vomiting, fever, and the presence of elevated hepatic transaminases.Conclusion:TAE is a safe and effective treatment for symptomatic hepatic hemangioma. The established nomogram performed well for the estimation of the effect of TAE in patients with hepatic hemangioma and can facilitate the selection of patients who would benefit most from the treatment.
Potential Biomarkers to Predict Acute Ischemic Stroke in Type 2 Diabetes
Authors: Moin Abu Saleh Md , Nandakumar Manjula , Al-Qaissi Ahmed , Sathyapalan Thozhukat , Atkin Stephen L. , Butler Alexandra E. 
Published: December 2021

Background and Purpose: Patients with type 2 diabetes (T2D) have increased risk of cardiovascular disease (CVD), encompassing myocardial infarction, stroke, and peripheral vascular disease. We hypothesized that those biomarkers indicative of acute ischemic stroke (AIS) seen in large vessel occlusion (LVO) may also be elevated in T2D and further enhanced by stress conditions; therefore, these proteins represent potentially predictive biomarkers for those T2D patients at high risk of AIS.Methods: We performed an exploratory proteomic analysis in control subjects (n = 23) versus those with type 2 diabetes (T2D) (n = 23) who underwent a hyperinsulinemic clamp study to transient severe hypoglycemia [blood glucose &lt;2.0 mmol/L (36 mg/dl)] in a prospective case-control study. We compared these proteins described as diagnostic and prognostic biomarkers for AIS due to LVO: lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE1), thrombospondin-1 (THBS1), pro-platelet basic protein (PPBP), and cadherin 1 (CDH1).Results: At baseline (BL), PPBP (p &lt; 0.05), THBS1 (p &lt; 0.05), and CDH1 (p &lt; 0.01) were elevated in T2D; LYVE1 was not different between controls and T2D subjects at BL or at subsequent timepoints. PPBP and THBS1 tended to increase at hypoglycemia in both cohorts, though reached significance only in controls (p &lt; 0.05), returning to BL levels post-hypoglycemia. CDH1 levels were higher in T2D at BL, at hypoglycemia and up to 2-h posthypoglycemia, thereafter reverting to BL levels.Conclusion: Elevated levels of PPBP, THBS1, and CDH1, circulatory proteins suggested as biomarkers of AIS due to LVO, may, in T2D patients, be prognostically indicative of a cohort of T2D patients at increased risk of ischaemic stroke. Prospective studies are needed to determine if this reflects future clinical risk.Clinical trial reg. no: NCT03102801.
Effects of Chronic Social Defeat Stress on Behavior and Dopamine Receptors in Adolescent Mice With 6-Hydroxydopamine Lesions of the Medial Prefrontal Cortex
Authors: Zhao Tong , Gao XiaoLei , Huang Guang-Biao 
Published: December 2021

Background: Social stress factors in schizophrenia have long-term effects, but will only induce symptoms in a portion of individuals, even if exposed to identical stress.Methods: In the current experiment, we examined mice with 6-hydroxydopamine (6-OHDA)-induced medial prefrontal cortical (mPFC) injury to select for members of a “stress-susceptible group,” and observed the changes in their behavior and the expression of D1 and D2 dopamine receptors in the amygdala and hippocampus.Results: We observed that after chronic social defeat stress, 72.6% of the 6-OHDA lesioned mice exhibited stress response to aggressors, compared to 52.3% of the blank control group. Both the 6-OHDA lesion + social defeat and social defeat groups exhibited anxiety and depression-like behavior. However, social cognitive impairment in the mice from the 6-OHDA lesion + social defeat group was more significant and the D1 expression levels in the amygdala were significantly decreased.Conclusion: These results suggest that the reason that adolescent mice with cortical injury were highly sensitive to defeat stress and had more prominent social cognitive impairment may be the decreased selectivity of D1 in the amygdala.
Induction of Relaxation by Autonomous Sensory Meridian Response
Authors: Sakurai Noriko , Ohno Ken , Kasai Satoshi , Nagasaka Kazuaki , Onishi Hideaki , Kodama Naoki 
Published: December 2021

Background: Autonomous sensory meridian response (ASMR) is used by young people to induce relaxation and sleep and to reduce stress and anxiety; it comprises somatosensation caused by audiovisual stimuli (triggers) that lead to positive emotions. Auditory stimuli play the most important role among the triggers involved in ASMR and have been reported to be more triggering than visual stimuli. On the other hand, classical music is also known to have a relaxing effect. This is the first study to clarify the difference in brain activation associated with relaxation effects between ASMR and classical music by limiting ASMR to auditory stimulation alone.Methods: Thirty healthy subjects, all over 20 years of age, underwent fMRI while listening to ASMR and classical music. We compared the differences in brain activation associated with classical music and ASMR stimulation. After the experiment, the subjects were administered a questionnaire on somatosensation and moods. After the experiment, the participants were asked whether they experienced ASMR somatosensation or frisson. They were also asked to rate the intensity of two moods during stimulation: “comfortable mood,” and “tingling mood”.Result: The results of the questionnaire showed that none of the participants experienced any ASMR somatosensation or frisson. Further, there was no significant difference in the ratings given to comfort mood, but there was a significant difference in those given to tingling mood. In terms of brain function, classical music and ASMR showed significant activation in common areas, while ASMR showed activation in more areas, with the medial prefrontal cortex being the main area of activation during ASMR.Conclusion: Both classical music and the ASMR auditory stimulus produced a pleasant and relaxed state, and ASMR involved more complex brain functions than classical music, especially the activation of the medial prefrontal cortex. Although ASMR was limited to auditory stimulation, the effects were similar to those of listening to classical music, suggesting that ASMR stimulation can produce a pleasant state of relaxation even if it is limited to the auditory component, without the somatic sensation of tingling. ASMR stimulation is easy to use, and appropriate for wellness purposes and a wide range of people.
Profiling of Differentially Expressed MicroRNAs in Saliva of Parkinson's Disease Patients
Authors: Jiang Yanyan , Chen Jing , Sun Yunchuang , Li Fan , Wei Luhua , Sun Wei , Deng Jianwen , Yuan Yun , Wang Zhaoxia 
Published: December 2021

Objective: This study aims to identify differentially expressed salivary miRNAs and validate the diagnostic potential for idiopathic Parkinson's disease (PD). Also, the disease specificity of candidate miRNAs was evaluated between PD, multiple system atrophy (MSA), and essential tremor (ET).Methods: We collected salivary samples from 50 PD, 20 ET, and 20 MSA patients, as well as 30 healthy controls (HCs). In the discovery phase, salivary miRNA microarray analysis was performed. In-silico analysis was used to investigate the target genes of differentially expressed miRNAs and clustered pathways. In validation phase, RT-qPCR was performed with samples from 30 PD patients and 30 HCs. Subsequently, we investigated candidate miRNAs in all recruited subjects. Receiver operating characteristic curve and Spearman correlation analysis was performed to determine diagnostic usefulness.Results: We identified 43 miRNAs that were differentially expressed between 5 PD patients and 5 HCs by miRNA microarray analysis. Computational analysis revealed the target genes were clustered in the pathways associated with ubiquitin protein ligase activity. The result of RT-qPCR showed that the miR-29a-3p and miR-29c-3p were found to be significantly downregulated (p = 0.004, p = 0.027), whereas the miR-6756-5p was significantly upregulated in 30 PD patients compared with 30 HCs (p = 0.032). The miR-29a-3p expression level in PD patients was significantly lower than ET patients (p = 0.035), but higher than MSA patients (p &lt; 0.0001). The diagnostic efficacy reached a little higher when the combination of miR-29a-3p and miR-29c-3p.Conclusion: The miRNA combination of salivary miR-29a-3p and miR-29c-3p has potential to be a diagnostic biomarker for idiopathic PD.
Staff and Facility Utilization in Direct Patient Transfer to the Comprehensive Stroke Center: Testing a Real-Time Location System for Automatic Patient Pathway Characterization
Authors: Moreira Tiago , Furnica Alexander , Daemen Elke , Mazya Michael V. , Sjöstrand Christina , Kaijser Magnus , Loenen Evert van 
Published: December 2021

Introduction: Starting reperfusion therapies as early as possible in acute ischemic strokes are of utmost importance to improve outcomes. The Comprehensive Stroke Centers (CSCs) can use surveys, shadowing personnel or perform journal analysis to improve logistics, which can be labor intensive, lack accuracy, and disturb the staff by requiring manual intervention. The aim of this study was to measure transport times, facility usage, and patient–staff colocalization with an automated real-time location system (RTLS).Patients and Methods: We tested IR detection of patient wristbands and staff badges in parallel with a period when the triage of stroke patients was changed from admission to the emergency room (ER) to direct admission to neuroradiology.Results: In total, 281 patients were enrolled. In 242/281 (86%) of cases, stroke patient logistics could be detected. Consistent patient–staff colocalizations were detected in 177/281 (63%) of cases. Bypassing the ER led to a significant decrease in median time neurologists spent with patients (from 15 to 9 min), but to an increase of the time nurses spent with patients (from 13 to 22 min; p = 0.036). Ischemic stroke patients used the most staff time (median 25 min) compared to hemorrhagic stroke patients (median 13 min) and stroke mimics (median 15 min).Discussion: Time spent with patients increased for nurses, but decreased for neurologists after direct triage to the CSC. While lower in-hospital transport times were detected, time spent in neuroradiology (CT room and waiting) remained unchanged.Conclusion: The RTLS could be used to measure the timestamps in stroke pathways and assist in staff allocation.
Facilitating Word Retrieval in Aphasia: Which Type of Cues for Which Aphasic Speakers?
Authors: Python Grégoire , Pellet Cheneval Pauline , Bonnans Caroline , Laganaro Marina 
Published: December 2021

Background: Even if both phonological and semantic cues can facilitate word retrieval in aphasia, it remains unclear if their respective effectiveness varies according to the underlying anomic profile.Aim: The aim of the present facilitation study is to compare the effect of phonological and semantic cues on picture naming accuracy and speed in different types of anomia.Methods: In the present within-subject design study, 15 aphasic persons following brain damage underwent picture naming paradigms with semantic cues (categorically- or associatively related) and phonological cues (initial phoneme presented auditorily, visually or both).Results: At the group level, semantic cueing was as effective as phonological cueing to significantly speed up picture naming. However, while phonological cues were effective regardless of the anomic profile, semantic cueing effects varied depending on the type of anomia. Participants with mixed anomia showed facilitation after both semantic categorical and associative cues, but individuals with lexical-phonological anomia only after categorical cues. Crucially, semantic cues were ineffective for participants with lexical-semantic anomia. These disparities were confirmed by categorical semantic facilitation decreasing when semantic/omission errors prevailed in the anomic profile, but increasing alongside phonological errors.Conclusion: The effectiveness of phonological vs semantic cues seems related to the underlying anomic profile: phonological cues benefit any type of anomia, but semantic cues only lexical-phonological or mixed anomia.
Influence of Atomoxetine on Relationship Between ADHD Symptoms and Prefrontal Cortex Activity During Task Execution in Adult Patients
Authors: Sugimoto Atsunori , Suzuki Yutaro , Yoshinaga Kiyohiro , Orime Naoki , Hayashi Taketsugu , Egawa Jun , Ono Shin , Sugai Takuro , Someya Toshiyuki 
Published: December 2021

Objective: We conducted this non-randomized prospective interventional study to clarify the relationship between improved attention-deficit hyperactivity disorder (ADHD) symptoms and regional brain activity.Methods: Thirty-one adult patients underwent near-infrared spectroscopy examinations during a go/no-go task, both before and 8 weeks after atomoxetine administration.Results: Clinical symptoms, neuropsychological results of the go/no-go task, and bilateral lateral prefrontal activity significantly changed. A positive correlation was observed between right dorsolateral prefrontal cortex activity and Conners’ Adult ADHD Rating Scales scores. Before atomoxetine administration, no correlations between prefrontal cortex activity and clinical symptoms were observed in all cases. When participants were divided into atomoxetine-responder and non-responder groups, a positive correlation was observed between prefrontal cortex activity and clinical symptoms in the non-responder group before treatment but not in the responder group, suggesting that non-responders can activate the prefrontal cortex without atomoxetine.Conclusions: Individuals with increased ADHD symptoms appear to recruit the right dorsolateral prefrontal cortex more strongly to perform the same task than those with fewer symptoms. In clinical settings, individuals with severe symptoms are often observed to perform more difficultly when performing the tasks which individuals with mild symptoms can perform easily. The atomoxetine-responder group was unable to properly activate the right dorsolateral prefrontal cortex when necessary, and the oral administration of atomoxetine enabled these patients to activate this region. In brain imaging studies of heterogeneous syndromes such as ADHD, the analytical strategy used in this study, involving drug-responsivity grouping, may effectively increase the signal-to-noise ratio.
Comparing the Performance of Two Radiomic Models to Predict Progression and Progression Speed of White Matter Hyperintensities
Authors: Shao Yuan , Ruan Jingru , Xu Yuyun , Shu Zhenyu , He Xiaodong 
Published: December 2021

Purpose: The aim of this study was to compare two radiomic models in predicting the progression of white matter hyperintensity (WMH) and the speed of progression from conventional magnetic resonance images.Methods: In this study, 232 people were retrospectively analyzed at Medical Center A (training and testing groups) and Medical Center B (external validation group). A visual rating scale was used to divide all patients into WMH progression and non-progression groups. Two regions of interest (ROIs)—ROI whole-brain white matter (WBWM) and ROI WMH penumbra (WMHp)—were segmented from the baseline image. For predicting WMH progression, logistic regression was applied to create radiomic models in the two ROIs. Then, age, sex, clinical course, vascular risk factors, and imaging factors were incorporated into a stepwise regression analysis to construct the combined diagnosis model. Finally, the presence of a correlation between radiomic findings and the speed of progression was analyzed.Results: The area under the curve (AUC) was higher for the WMHp-based radiomic model than the WBWM-based radiomic model in training, testing, and validation groups (0.791, 0.768, and 0.767 vs. 0.725, 0.693, and 0.691, respectively). The WBWM-based combined model was established by combining age, hypertension, and rad-score of the ROI WBWM. Also, the WMHp-based combined model is built by combining the age and rad-score of the ROI WMHp. Compared with the WBWM-based model (AUC = 0.779, 0.716, 0.673 in training, testing, and validation groups, respectively), the WMHp-based combined model has higher diagnostic efficiency and better generalization ability (AUC = 0.793, 0.774, 0.777 in training, testing, and validation groups, respectively). The speed of WMH progression was related to the rad-score from ROI WMHp (r = 0.49) but not from ROI WBWM.Conclusion: The heterogeneity of the penumbra could help identify the individuals at high risk of WMH progression and the rad-score of it was correlated with the speed of progression.
Temporal Clustering of Skin Sympathetic Nerve Activity Bursts in Acute Myocardial Infarction Patients
Authors: Liu Chun , Lee Chien-Hung , Lin Shien-Fong , Tsai Wei-Chung 
Published: December 2021

Backgrounds: Acute myocardial infarction (AMI) affects the autonomic nervous system (ANS) function. The aim of our study is to detect the particular patterns of ANS regulation in AMI. We hypothesize that altered ANS regulation in AMI patients causes synchronized neural discharge (clustering phenomenon) detected by non-invasive skin sympathetic nerve activity (SKNA).Methods: Forty subjects, including 20 AMI patients and 20 non-AMI controls, participated in the study. The wide-band bioelectrical signals (neuECG) were continuously recorded on the body surface for 5 min. SKNA was signal processed to depict the envelope of SKNA (eSKNA). By labeling the clusters, the AMI subjects were separated into non-AMI, non-cluster appearing (AMINCA), and cluster appearing (AMICA) groups.Results: The average eSKNA was significantly correlated with HRV low-frequency (LF) power (rho = −0.336) and high-frequency power (rho = −0.372). The cross-comparison results demonstrated that eSKNA is a valid surrogate marker to assess ANS in AMI patients. The frequency of cluster occurrence was 0.01–0.03 Hz and the amplitude was about 3 μV. The LF/HF ratio of AMICA (median: 1.877; Q1–Q3: 1.483–2.413) revealed significantly lower than AMINCA (median: 3.959; Q1–Q3: 1.840–6.562). The results suggest that the SKNA clustering is a unique temporal pattern of ANS synchronized discharge, which could indicate the lower sympathetic status (by HRV) in AMI patients.Conclusion: This is the first study to identify SKNA clustering phenomenon in AMI patients. Such a synchronized nerve discharge pattern could be detected with non-invasive SKNA signals. SKNA temporal clustering could be a novel biomarker to classify ANS regulation ability in AMI patients.Clinical and Translational Significance: SKNA is higher in AMI patients than in control and negatively correlates with parasympathetic parameters. SKNA clustering is associated with a lower LF/HF ratio that has been shown to correlate with sudden cardiac death in AMI. The lack of SKNA temporal clustering could indicate poor ANS regulation in AMI patients.