bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of MAPK8IP3 Affects Endocytosis in Neurons
Authors: Snead Amanda M. , Gowrishankar Swetha
Published: June 2022

Perturbations in endo-lysosomal trafficking pathways are linked to many neurodevelopmental and neurodegenerative diseases. Of relevance to our current study, MAPK8IP3/JIP3, a brain enriched putative adaptor between lysosomes and motors has been previously implicated as a key regulator of axonal lysosome transport. Since de novo variants in MAPK8IP3 have recently been linked to a neurodevelopmental disorder with intellectual disability, there is a need to better understand the functioning of this protein in human neurons. To this end, using induced neurons (i3Neurons) derived from human iPSCs lacking MAPK8IP3, we demonstrate that loss of hMAPK8IP3 affects endocytic uptake in neurons but does not affect the proteolytic activity of lysosomes in neuronal cell bodies. Our findings indicate that MAPK8IP3 may be a regulator of bulk endocytosis in neurons and that altered endocytic uptake may play a role in MAPK8IP3-linked neurodevelopmental disorders.
Principal Component Analysis of Oxford Cognitive Screen in Patients With Stroke
Authors: Iosa Marco , Demeyere Nele , Abbruzzese Laura , Zoccolotti Pierluigi , Mancuso Mauro
Published: June 2022

Cognitive deficits occur in most patients with stroke and are the important predictors of adverse long-term outcome. Early identification is fundamental to plan the most appropriate care, including rehabilitation and discharge decisions. The Oxford Cognitive Screen (OCS) is a simple, valid, and reliable tool for the assessment of cognitive deficits in patients with stroke. It contains 10 subtests, providing 14 scores referring to 5 theoretically derived cognitive domains: attention, language, number, praxis, and memory. However, an empirical verification of the domain composition of the OCS subtests in stroke data is still lacking in the literature. A principal component analysis (PCA) was performed on 1,973 patients with stroke who were enrolled in OCS studies in the UK and in Italy. A number of six main components were identified relating to the domains of language and arithmetic, memory, visuomotor ability, orientation, spatial exploration, and executive functions. Bootstrapped split-half reliability analysis on patients and comparison between patients and 498 healthy participants, as that between patients with left and right hemisphere damage, confirmed the results obtained by the principal component analysis. A clarification about the contribution of each score to the theoretical original domains and to the components identified by the PCA is provided with the aim to foster the usability of OCS for both clinicians and researchers.
Association of Pre-stroke Frailty With Prognosis of Elderly Patients With Acute Cerebral Infarction: A Cohort Study
Authors: Yang Fuxia , Li Nan , Yang Lu , Chang Jie , Yan Aijuan , Wei Wenshi
Published: June 2022

Background

Frailty is a state of cumulative degradation of physiological functions that leads to adverse outcomes such as disability or mortality. Currently, there is still little understanding of the prognosis of pre-stroke frailty status with acute cerebral infarction in the elderly.

Objective

We investigated the association between pre-stroke frailty status, 28-day and 1-year survival outcomes, and functional recovery after acute cerebral infarction.

Methods

Clinical data were collected from 314 patients with acute cerebral infarction aged 65–99 years. A total of 261 patients completed follow-up in the survival cohort analysis and 215 patients in the functional recovery cohort analysis. Pre-stroke frailty status was assessed using the FRAIL score, the prognosis was assessed using the modified Rankin Scale (mRS), and disease severity using the National Institutes of Health Stroke Scale (NIHSS).

Results

Frailty was independently associated with 28-day mortality in the survival analysis cohort [hazard ratio (HR) = 4.30, 95% CI 1.35–13.67, p = 0.014]. However, frailty had no independent effect on 1-year mortality (HR = 1.47, 95% CI 0.78–2.79, p = 0.237), but it was independently associated with advanced age, the severity of cerebral infarction, and combined infection during hospitalization. Logistic regression analysis after adjusting for potential confounders in the functional recovery cohort revealed frailty, and the NIHSS score was significantly associated with post-stroke severe disability (mRS > 2) at 28 days [pre-frailty adjusted odds ratio (aOR): 8.86, 95% CI 3.07–25.58, p < 0.001; frailty aOR: 7.68, 95% CI 2.03–29.12, p = 0.002] or 1 year (pre-frailty aOR: 8.86, 95% CI 3.07–25.58, p < 0.001; frailty aOR: 7.68, 95% CI 2.03–29.12, p = 0.003).

Conclusions

Pre-stroke frailty is an independent risk factor for 28-day mortality and 28-day or 1-year severe disability. Age, the NIHSS score, and co-infection are likewise independent risk factors for 1-year mortality.
Respective Contributions of Instrumented 3D Gait Analysis Data and Tibial Motor Nerve Block on Presurgical Spastic Equinus Foot Assessment: A Retrospective Study of 40 Adults
Authors: Cormier Camille , Sourisseau Clément , Montane Emmeline , Scandella Marino , Castel-Lacanal Evelyne , Boissezon Xavier De , Marque Philippe , Gasq David
Published: June 2022

Spastic equinus foot is a common deformity in neurologic patients who compromise walking ability. It is related to the imbalance between weak dorsiflexion and overactive plantar flexor muscles. To achieve the best functional results after surgical management, the challenge is to identify the relevant components involved in the deformity using several methods, namely, examination in the supine position, motor nerve blocks allowing transient anesthesia of suspected overactive muscles, and kinematic and electromyographic data collected during an instrumented 3D gait analysis. The procedure is not standardized; its use varies from one team to another. Access to gait analysis laboratories is limited, and some teams do not perform motor nerve blocks. When both examinations are available, instrumental data from the instrumented 3D gait analysis can be used to specify muscle targets for motor blocks, but data collected from both examinations are sometimes considered redundant.

This retrospective cohort analysis compared examination in the supine position, temporary motor nerve blocks, and instrumented 3D gait analysis data in 40 adults after brain or spinal cord injuries. Clinical data collected before motor nerve block was not associated with instrumental data to assess calf muscle's overactivity and tibialis anterior function. Improvement of ankle dorsiflexion in the swing phase after tibial motor nerve block was associated with soleus spastic co-contraction during this phase corroborating its involvement in ankle dorsiflexion defects. This study showed the relevance of tibial motor nerve block to remove spastic calf dystonia and facilitate the assessment of calf contracture. It also underlined the need for complementary and specific analyses of the tibialis anterior abnormal activation pattern after motor nerve block to confirm or deny their pathological nature.
Interictal Discharge Pattern in Preschool-Aged Children With Tuberous Sclerosis Complex Before and After Resective Epilepsy Surgery
Authors: Yuan Liu , Wang Yangshuo , Cheng Shuhua , Zhang Junchen , Zhang Shaohui , Liu Tinghong , Zhang Guojun , Liang Shuli
Published: June 2022

Objective

To analyze the interictal discharge (IID) patterns on pre-operative scalp electroencephalogram (EEG) and compare the changes in IID patterns after removal of epileptogenic tubers in preschool children with tuberous sclerosis complex (TSC)-related epilepsy.

Methods

Thirty-five preschool children who underwent resective surgery for TSC-related epilepsy were enrolled retrospectively, and their EEG data collected before surgery to 3 years after surgery were analyzed.

Results

Twenty-three (65.7%) patients were seizure-free post-operatively at 1-year follow-up, and 37–40% of post-operative patients rendered non-IID on scalp EEGs, and patients with focal IIDs or generalized IID patterns on pre-operative EEG presented a high percentage of normal post-operative scalp EEGs. IID patterns on pre-operative scalp EEGs did not influence the outcomes of post-operative seizure controls, while patients with non-IID and focal IID on post-operative EEGs were likely to achieve post-operative seizure freedom. Patients with new focal IIDs presented a significantly lower percentage of seizure freedom than those without new focal IIDs on post-operative EEGs at 3-year follow-up.

Conclusion

Over 1/3 children with TSC presented normal scalp EEGs after resective epileptsy surgery. Patients with post-operative seizure freedom were more likely to have non-IIDs on post-operative EEGs. New focal IIDs were negative factors for seizure freedom at the 3-year follow-up.
Predicting Global Functional Outcomes Among Post-traumatic Epilepsy Patients After Moderate-to-Severe Traumatic Brain Injury: Development of a Prognostic Model
Authors: Yu Tingting , Liu Xiao , Sun Lei , Lv Ruijuan , Wu Jianping , Wang Qun
Published: June 2022

Objective

The development of post-traumatic epilepsy (PTE) following traumatic brain injury (TBI) is associated with unfavorable functional outcomes, and the global function of PTE patients might change dynamically overtime. Predicting the long-term functional outcomes of patients with PTE may help to develop accurate rehabilitation programs and improve their quality of life. Based on this, the objective of this study is to use clinical data to derive and validate a model for predicting the functional outcomes of patients with PTE after moderate-to-severe TBI.

Methods

This study retrospectively analyzed 721 patients with PTE after moderate-to-severe TBI in the Epilepsy Centre, Beijing Tiantan Hospital, from January 2013 to December 2018. All patients had favorable global function as indicated by the Glasgow Outcome Scale-Extended (GOSE) at the time of their first late post-traumatic seizure (PTS) onset, and the 5-year global function after the first late PTS onset was chosen as the principal outcome of interest. To identify possible predictors for the global functional outcomes, univariate and multivariate logistic regression techniques were used. A prognostic model was established using these identified predictors, the internal validation with the bootstrapping method was performed, and the model was then visualized as a graphical score chart.

Results

The 5-year global functional outcome of 98 (13.59%) patients was unfavorable, and the temporal lobe lesion was found as the strongest predictor of unfavorable outcomes. The final prognostic model also included the following other predictors: gender, age at TBI, multiple injuries, the severity of TBI, and latency of PTE. Discrimination was satisfactory with C-statistic of 0.754 (0.707 – 0.800), the goodness-of-fit test indicated good calibration (P = 0.137), and the C-statistic was 0.726 for internal validation. A graphical score chart was also constructed to provide the probability of an unfavorable 5-year global functional outcomes more readily.

Conclusions

Clearer treatment strategies are essential to help ameliorate the global functional outcomes of patients with PTE. Our proposed prognostic model has significant potential to be used in the clinic for predicting global functional outcomes among patients with PTE after moderate-to-severe TBI.
Effectiveness and Safety of Oxcarbazepine vs. Levetiracetam as Monotherapy for Infantile Focal Epilepsy: A Longitudinal Cohort Study
Authors: Zhao Binyang , Liao Shuang , Zhong Xuefei , Luo Yuanyuan , Hong Siqi , Cheng Min , Zhang Jie , Li Tingsong , Jiang Li
Published: June 2022

Objective

This study aimed to compare the effectiveness and safety of oxcarbazepine (OXC) vs. levetiracetam (LEV) for treating infantile focal epilepsy in a longitudinal cohort study.

Methods

We enrolled 187 consecutive patients aged 2–24 months who received OXC or LEV as initial monotherapy; 161 patients completed the study. The longitudinal analysis involved anti-seizure medication (ASM) responsiveness, safety, the establishment of epilepsy syndrome, and etiology over a median follow-up of 2 years (interquartile range [IQR] 1.6–2.4). The relative efficacy and retention rates of OXC vs. LEV were evaluated using generalized linear regression models and the Cox proportional hazards model.

Results

The 161 patients who completed the study had comparable baseline demographics and clinical variables between the OXC group (n = 83) and LEV group (n = 78). Overall, the mean age at onset was 6 months (IQR 4.3–9). The most common epilepsy syndrome was self-limited familial/non-familial infantile epilepsy (54.7%). Epilepsy was related to genetic and unknown causes in 34.2 and 52.2% of the patients, respectively. OXC achieved significantly higher responses than LEV for seizure freedom (risk ratio [RR] = 1.71, 95% confidence interval [CI] = 1.28–2.73, P < 0.001) and 12-month retention rate after onset (hazard ratio [HR] = 1.84, 95% CI = 1.15–2.95, P = 0.007). Moreover, OXC showed more obvious effects for patients aged < 1 year diagnosed with self-limited familial/non-familial infantile epilepsy and non-syndromic epilepsy with genetic or unknown causes. The adverse events related to both OXC and LEV were well-tolerated.

Significance

OXC could be an alternative to LEV for treating infantile focal epilepsy. OXC monotherapy can be considered first-line treatment for patients aged <12 months and those with epilepsy without developmental and epileptic encephalopathy.
Comparison of CNN-Learned vs. Handcrafted Features for Detection of Parkinson's Disease Dysgraphia in a Multilingual Dataset
Authors: Galaz Zoltan , Drotar Peter , Mekyska Jiri , Gazda Matej , Mucha Jan , Zvoncak Vojtech , Smekal Zdenek , Faundez-Zanuy Marcos , Castrillon Reinel , Orozco-Arroyave Juan Rafael , Rapcsak Steven , Kincses Tamas , Brabenec Lubos , Rektorova Irena
Published: June 2022

Parkinson's disease dysgraphia (PDYS), one of the earliest signs of Parkinson's disease (PD), has been researched as a promising biomarker of PD and as the target of a noninvasive and inexpensive approach to monitoring the progress of the disease. However, although several approaches to supportive PDYS diagnosis have been proposed (mainly based on handcrafted features (HF) extracted from online handwriting or the utilization of deep neural networks), it remains unclear which approach provides the highest discrimination power and how these approaches can be transferred between different datasets and languages. This study aims to compare classification performance based on two types of features: features automatically extracted by a pretrained convolutional neural network (CNN) and HF designed by human experts. Both approaches are evaluated on a multilingual dataset collected from 143 PD patients and 151 healthy controls in the Czech Republic, United States, Colombia, and Hungary. The subjects performed the spiral drawing task (SDT; a language-independent task) and the sentence writing task (SWT; a language-dependent task). Models based on logistic regression and gradient boosting were trained in several scenarios, specifically single language (SL), leave one language out (LOLO), and all languages combined (ALC). We found that the HF slightly outperformed the CNN-extracted features in all considered evaluation scenarios for the SWT. In detail, the following balanced accuracy (BACC) scores were achieved: SL—0.65 (HF), 0.58 (CNN); LOLO—0.65 (HF), 0.57 (CNN); and ALC—0.69 (HF), 0.66 (CNN). However, in the case of the SDT, features extracted by a CNN provided competitive results: SL—0.66 (HF), 0.62 (CNN); LOLO—0.56 (HF), 0.54 (CNN); and ALC—0.60 (HF), 0.60 (CNN). In summary, regarding the SWT, the HF outperformed the CNN-extracted features over 6% (mean BACC of 0.66 for HF, and 0.60 for CNN). In the case of the SDT, both feature sets provided almost identical classification performance (mean BACC of 0.60 for HF, and 0.58 for CNN).
Deep Learning-Based Automated Detection of Arterial Vessel Wall and Plaque on Magnetic Resonance Vessel Wall Images
Authors: Xu Wenjing , Yang Xiong , Li Yikang , Jiang Guihua , Jia Sen , Gong Zhenhuan , Mao Yufei , Zhang Shuheng , Teng Yanqun , Zhu Jiayu , He Qiang , Wan Liwen , Liang Dong , Li Ye , Hu Zhanli , Zheng Hairong , Liu Xin , Zhang Na
Published: June 2022

Purpose

To develop and evaluate an automatic segmentation method of arterial vessel walls and plaques, which is beneficial for facilitating the arterial morphological quantification in magnetic resonance vessel wall imaging (MRVWI).

Methods

MRVWI images acquired from 124 patients with atherosclerotic plaques were included. A convolutional neural network-based deep learning model, namely VWISegNet, was used to extract the features from MRVWI images and calculate the category of each pixel to facilitate the segmentation of vessel wall. Two-dimensional (2D) cross-sectional slices reconstructed from all plaques and 7 main arterial segments of 115 patients were used to build and optimize the deep learning model. The model performance was evaluated on the remaining nine-patient test set using the Dice similarity coefficient (DSC) and average surface distance (ASD).

Results

The proposed automatic segmentation method demonstrated satisfactory agreement with the manual method, with DSCs of 93.8% for lumen contours and 86.0% for outer wall contours, which were higher than those obtained from the traditional U-Net, Attention U-Net, and Inception U-Net on the same nine-subject test set. And all the ASD values were less than 0.198 mm. The Bland–Altman plots and scatter plots also showed that there was a good agreement between the methods. All intraclass correlation coefficient values between the automatic method and manual method were greater than 0.780, and greater than that between two manual reads.

Conclusion

The proposed deep learning-based automatic segmentation method achieved good consistency with the manual methods in the segmentation of arterial vessel wall and plaque and is even more accurate than manual results, hence improved the convenience of arterial morphological quantification.
Listening Over Time: Single-Trial Tonic and Phasic Oscillatory Alpha-and Theta-Band Indicators of Listening-Related Fatigue
Authors: Hunter Cynthia R.
Published: June 2022

Objectives

Listening effort engages cognitive resources to support speech understanding in adverse listening conditions, and leads to fatigue over the longer term for people with hearing loss. Direct, neural measures of listening-related fatigue have not been developed. Here, event-related or phasic changes in alpha and theta oscillatory power during listening were used as measures of listening effort, and longer-term or tonic changes over the course of the listening task were assessed as measures of listening-related fatigue. In addition, influences of self-reported fatigue and degree of hearing loss on tonic changes in oscillatory power were examined.

Design

Participants were middle-aged adults (age 37–65 years; n = 12) with age-appropriate hearing. Sentences were presented in a background of multi-talker babble at a range of signal-to-noise ratios (SNRs) varying around the 80 percent threshold of individual listeners. Single-trial oscillatory power during both sentence and baseline intervals was analyzed with linear mixed-effect models that included as predictors trial number, SNR, subjective fatigue, and hearing loss.

Results

Alpha and theta power in both sentence presentation and baseline intervals increased as a function of trial, indicating listening-related fatigue. Further, tonic power increases across trials were affected by hearing loss and/or subjective fatigue, particularly in the alpha-band. Phasic changes in alpha and theta power generally tracked with SNR, with decreased alpha power and increased theta power at less favorable SNRs. However, for the alpha-band, the linear effect of SNR emerged only at later trials.

Conclusion

Tonic increases in oscillatory power in alpha- and theta-bands over the course of a listening task may be biomarkers for the development of listening-related fatigue. In addition, alpha-band power as an index of listening-related fatigue may be sensitive to individual differences attributable to level of hearing loss and the subjective experience of listening-related fatigue. Finally, phasic effects of SNR on alpha power emerged only after a period of listening, suggesting that this measure of listening effort could depend on the development of listening-related fatigue.
Novel Strategies for Assessing Associations Between Selenium Biomarkers and Cardiometabolic Risk Factors: Concentration, Visit-to-Visit Variability, or Individual Mean? Evidence From a Repeated-Measures Study of Older Adults With High Selenium
Authors: Li Ang , Zhou Quan , Mei Yayuan , Zhao Jiaxin , Zhao Meiduo , Xu Jing , Ge Xiaoyu , Xu Qun
Published: June 2022

Background and Aims

Previous studies have focused only on the cardiometabolic effects of selenium concentrations. We explored whether selenium levels and their visit-to-visit variability (VVV) and individual mean (IM) are independently associated with cardiometabolic risk factors.

Methods

A three-wave repeated-measures study of older adults with high selenium (n = 201) was conducted in Beijing from 2016 to 2018. Whole blood selenium and urinary selenium concentrations were measured. VVV and IM were used to profile the homeostasis of the selenium biomarkers. Four indicators, namely standard deviation, coefficient of variation, average real variability, and variability independent of the mean, were employed to characterize VVV. We considered 13 cardiometabolic factors: four lipid profile indicators, three blood pressure indices, glucose, uric acid, waistline, hipline, waist-hip ratio, and sex-specific metabolic syndrome score. Linear mixed-effects regression models with random intercepts for the participants were employed to explore the associations of the selenium concentrations, VVV, and IM with the cardiometabolic factors.

Results

The geometric mean whole blood and urinary selenium levels were 134.30 and 18.00 μg/L, respectively. Selenium concentrations were significantly associated with numerous cardiometabolic factors. Specifically, whole blood selenium was positively associated with total cholesterol [0.22, 95% confidence interval (CI): 0.12, 0.33], low-density lipoprotein cholesterol (LDL-C; 0.28, 95% CI: 0.13, 0.42), glucose (0.22, 95% CI: 0.10, 0.34), and uric acid (0.16, 95% CI: 0.04, 0.28). After adjustment for VVV, the IM of whole blood selenium was positively correlated with total cholesterol (0.002, 95% CI: 0.001, 0.004), triglycerides (0.007, 95% CI: 0.004, 0.011), and LDL-C (0.002, 95% CI: 0.000, 0.004). However, we did not observe any robust associations between the VVV of the selenium biomarkers and cardiometabolic risk factors after adjustment for IM.

Conclusion

Our findings suggest that selenium concentrations and their IMs are significantly associated with cardiometabolic risk factors among older adults with high selenium. Longer repeated-measures studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.
Green Tea Intake and Parkinson's Disease Progression: A Mendelian Randomization Study
Authors: Li Chunyu , Lin Junyu , Yang Tianmi , Shang Huifang
Published: June 2022

Epidemiological studies have suggested green tea intake was associated with a reduced risk of Parkinson's disease (PD). However, whether green tea intake has an effect on PD progression is unknown. To evaluate the role of green tea intake in PD progression, we conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of green tea intake (N = 64,949), age at onset (N = 28,568) and progression (N = 4,093) of PD. One standard deviation increase in genetically determined green tea intake was significantly associated with slower progression to dementia (OR: 0.87, 95% CI: 0.81–0.94, P: 3.48E−04) after the Bonferroni correction. Meanwhile, higher green tea intake was nominally associated with slower progression to depression, and lower risk of dementia, depression, hyposmia and insomnia at baseline. The results were robust under all sensitivity analyses. These results might facilitate novel therapeutic targets to slow down the progression of PD in clinical trials, and have clinical implications for patients with PD.
The Correlation of Total Percent Fat With Alterations in Cholesterol and Triglycerides in Adults
Authors: Sun Juan , Zhang Zimu , Liu Zhen , Li Jie , Kang Weiming
Published: June 2022

Background

To evaluate the detailed relationship between total percent fat (TPF) and cardiovascular disease (CVD)-related lipid biomarkers among adults and find a non-invasive indicator for screening and monitoring of the high CVD risk population.

Methods

Data of 13,160 adults were obtained from the National Health and Examination Survey (NHANES) from 1999 to 2018. TPF was assessed by dual-energy x-ray absorptiometry (DXA), and CVD-related lipid biomarkers included total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Multivariable linear regression models were used to examine associations between TPF with four kinds of lipid biomarkers, and smooth curve fittings and generalized additive models were used to address the non-linear relationship between them. The inflection points were calculated by the recursive algorithm when non-linearities were detected and then weighted two-piecewise linear regression models were constructed.

Results

In multivariable regression, increasing TPF was positively associated with TC, TG, and LDL-C and negatively with HDL-C (all p < 0.001). In addition, the non-linear relationships between them were also identified by generalized additive models and smooth curve fittings. When further stratified TPF by sex, the fitted smooth curves were nearly inverted U-shaped and U-shaped curves, the inflection points were calculated, and the weighted two-piecewise linear regression models were constructed, respectively. The same results existed between android percent fat and these four lipid biomarkers.

Conclusions

Total percent fat was significantly associated with CVD-related lipid biomarkers in adults, positively with TC, TG, and LDL-C and negatively with HDL-C. It could be used as a non-invasive screener and monitor of high CVD risk population when their TPF values were less than the inflection points.
Four-Week Supplementation of Water-Soluble Tomato Extract Attenuates Platelet Function in Chinese Healthy Middle-Aged and Older Individuals: A Randomized, Double-Blinded, and Crossover Clinical Trial
Authors: Tian Zezhong , Fan Die , Li Kongyao , Zhao Dan , Liang Ying , Ji Qiuhua , Gao Xiaoli , Ma Xilin , Zhao Yimin , Mao Yuheng , Meng Huicui , Yang Yan
Published: June 2022

Background and Aims

Platelets are linked to atherosclerotic development and pathological thrombosis. Single dose of water-soluble tomato extract (WTE) which is a natural extraction can exert anti-platelet effects after 3 or 7 h in British healthy people. However, the effects of WTE supplementation on platelet function in Chinese healthy middle-aged and older individuals have not been studied, and the effects or safety of 4-week WTE supplementation also remain unclear. The present study aims to determine the effects of WTE on platelet function, and explore the safety of 4-week WTE supplementation in Chinese healthy middle-aged and older individuals.

Methods

A randomized, double-blinded, and crossover clinical trial was conducted. Firstly, 105 individuals were randomly divided into two groups that received WTE (150 mg/day) or placebo for 4 weeks. Then, after a washout period of 2 weeks, two groups exchanged groups and continued for another 4-week intervention. Platelet aggregation, P-selectin, activated GPIIbIIIa, plasma platelet factor 4 (PF4), β-thromboglobulin (β-TG), and thromboxane B2 (TXB2) were tested at baseline, 4, 6, and 10 weeks.

Results

Compared with the placebo group, 150 mg/day WTE supplement for 4 weeks significantly reduced ADP-induced or collagen-induced platelet aggregation (−10.8 ± 1.8 or −3.9 ± 1.5%, P < 0.05), ADP-induced or collagen-induced platelet P-selectin expression (−6.9 ± 1.5 or −6.6 ± 1.3%, P < 0.05), ADP-induced or collagen-induced activated GPIIbIIIa (−6.2 ± 2.0 or −3.8 ± 2.0%, P < 0.05). Besides, 4-week intervention of 150 mg WTE per day also resulted in significant reductions in plasma PF4 (−120.6 ± 33.2 ng/mL, P < 0.05) and β-TG (−129.7 ± 27.5 ng/mL, P < 0.05) and TXB2 (−42.0 ± 4.0 ng/mL, P < 0.05), while had no effects on coagulation function and liver or renal function. Interestingly, 2-week washout period is enough to reverse the inhibitory effect of 4-week WTE supplementation on platelet function.

Conclusion

WTE supplementation for 4 weeks could moderately reduce platelet activation, aggregation, and granule secretion in Chinese healthy middle-aged and older individuals, and these effects are safe. After 2-week washout period, the inhibitory effect of 4-week WTE on platelet function can be eliminated.

Clinical Trial Registration

[http://www.chictr.org.cn/], identifier [ChiCTR-POR-17012927].
Association Between the Children's Dietary Inflammatory Index (C-DII) and Markers of Inflammation and Oxidative Stress Among Children and Adolescents: NHANES 2015-2018
Authors: Zhang Chuang , Ren Weirui , Li Meng , Wang Wenbo , Sun Chi , Liu Lin , Fang Yanbin , Liu Lin , Yang Xiaofeng , Zhang Xiangjian , Li Suolin
Published: June 2022

Objectives

To explore the association of Children's Dietary Inflammatory Index (C-DII) scores with inflammation and markers of inflammatory factors in children and adolescents.

Methods

Data on dietary nutrient intake, markers of inflammation (ferritin, alkaline phosphatase, C-reactive protein (CRP), absolute neutrophil cell count and lymphocyte count) and oxidative stress (serum bilirubin, albumin, and iron) were available for participants aged 6–19 years (n = 1281). Each participant's C-DII score was calculated based on a 24-h diet and recall. Generalized linear models were applied to examine associations between C-DII and markers of inflammation and oxidative stress, while adjusting for covariates. Restricted cubic splines were used to explore the dose-response association of C-DII scores with indicators of inflammatory oxidative stress. Akaike's Information Criterionwas applied to compare the performance of linear and non-linear models.

Results

After adjusting for potential confounders, quantile regression results showed that when comparing C-DII quartile 4 (most pro-inflammatory) and quartile 1 (most anti-inflammatory), lymphocytes, ferritin, CRP were statistically significant differences in serum bilirubin, albumin and serum iron (P < 0.05). The C-DII score showed a non-linear relationship with inflammatory oxidative stress indicators. Overweight/obese children and adolescents who ate a high pro-inflammatory diet were more likely to have higher levels of inflammatory cytokines (P = 0.002).

Conclusions

The dietary inflammatory index in children is associated with markers of chronic inflammation and oxidative stress. A pro-inflammatory diet resulted in increased serum concentrations of these markers, implying that early dietary interventions have implications for reducing chronic inflammation and oxidative stress in children and adolescents.
Effect of Polysaccharide Extracted From Gynostemma Pentaphyllum on the Body Weight and Gut Microbiota of Mice
Authors: Li Shiwei , Wang Yingna , Dun Weipeng , Han Wanqing , Ning Tao , Sun Qi , Wang Zichao
Published: June 2022

Researchers have investigated the role of polysaccharides in disease treatment via gut microbiota regulation but ignore their function in disease prevention and physique enhancement. In this work, a Gynostemma pentaphyllum polysaccharide (GPP) was tested by methyl thiazolyl tetrazolium (MTT) assay and proved to be safe to Caco-2 cells. Animal experiments showed that the administration of GPP for 3 weeks decreased the body weight gain of mice from 15.4 ± 1.7 to 12.2 ± 1.8 g in a concentration-dependent manner. Analysis of short-chain fatty acids (SCFAs) indicated that GPP increased the levels of acetate, propionate, butyrate, and total SCFAs in the cecum contents of normal mice. Furthermore, GPP improved the species richness and abundance in the gut microbiota but reduced the Firmicutes/Bacteroidetes ratio from 0.8021 to 0.3873. This work provides a basis for incorporating GPP into diet to prevent or mitigate the occurrence of obesity via gut microbiota regulation.
FBXW7 and Its Downstream NOTCH Pathway Could be Potential Indicators of Organ-Free Metastasis in Colorectal Cancer
Authors: Li Dongzheng , Jiang Shiye , Zhou Xin , Si Chengshuai , Shao Peng , Jiang Qian , Zhu Liuqing , Shen Lu , Meng Qi , Yin Jiani C. , Shao Yang , Sun Yueming , Yang Liu
Published: June 2022

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally. Metastasis is associated with a poor prognosis, yet the underlying molecular mechanism(s) remained largely unknown. In this study, a total of 85 CRC patients were included and the primary tumor lesions were evaluated by next-generation sequencing using a targeted panel for genetic aberrations. Patients were sub-divided according to their metastasis pattern into the non-organ metastases (Non-OM) and organ metastases (OM) groups. By comparing the genetic differences between the two groups, we found that mutations in FBXW7 and alterations in its downstream NOTCH signaling pathway were more common in the Non-OM group. Moreover, correlation analysis suggested that FBXW7 mutations were independent of other somatic alterations. The negative associations of alterations in FBXW7 and its downstream NOTCH signaling pathway with CRC organ metastasis were validated in a cohort of 230 patients in the TCGA CRC dataset. Thus, we speculated that the genomic alterations of FBXW7/NOTCH axis might be an independent negative indicator of CRC organ metastases.
Cumulative Scoring Systems and Nomograms for Predicating Survival in Patients With Glioblastomas: A Study Based on Peripheral Inflammatory Markers
Authors: Yang Chao , Lan Tian , Wang Yi , Huang Wen-Hong , Li Si-Man , Li Jie , Li Feng-Ping , Li Yi-Rong , Wang Ze-Fen , Li Zhi-Qiang
Published: June 2022

Inflammation is a hallmark of cancers. The purpose of the present study was to evaluate the prognostic potential of hematological inflammatory markers in glioblastoma multiforme (GBM) patients. The clinical data of 99 patients with lower-grade gliomas and 88 patients with GBMs were retrospectively analyzed. The optimal cutoff values for peripheral markers were determined by X-tile. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify markers with prognostic significance. Several scoring systems were constructed by combining these prognostic markers. The predictive accuracies of nomograms incorporating these scoring systems were evaluated by Harrell’s concordance index and receiver operating characteristic curve analysis. GBM patients exhibited higher neutrophil counts (p=0.001), neutrophil-to-lymphocyte ratio (NLR) (p<0.001), and platelet-to-lymphocyte ratio (PLR) (p=0.001), as well as lower lymphocyte counts (p=0.023), lymphocyte-to-monocyte ratio (LMR) (p=0.015), and albumin-to-globulin ratio (AGR) (p=0.003) than those with lower-grade gliomas. Multivariate analysis indicated that a high NLR (> 2.0) (Hazard ratio[HR]=2.519, 95% confidence interval (CI): 1.220-5.204, p=0.013), low LMR (< 2.3) (HR=2.268, 95%CI: 1.172-4.386, p=0.015), or low AGR (< 1.7) (HR=2.924, 95%CI: 1.389-6.135, p=0.005) were associated with poor overall survival in GBM patients. The scoring systems of AGR-NLR, AGR-LMR, and LMR-NLR were associated with GBM survival. The nomogram integrating AGR-NLR score had the best efficacy in predicting GBM survival (c-index=0.874). Pretreatment scores of AGR-NLR, AGR-LMR, and LMR-NLR may serve as prognostic factors for GBM patients, and a nomogram integrating AGR-NLR may provide a reliable tool to facilitate personalized preoperative evaluations.
Indocyanine Green Fluorescence Using in Conduit Reconstruction for Patients With Esophageal Cancer to Improve Short-Term Clinical Outcome: A Meta-Analysis
Authors: Hong Zhi-Nuan , Huang Liqin , Zhang Weiguang , Kang Mingqiang
Published: June 2022

Objectives

This meta-analysis evaluated the short-term safety and efficacy of indocyanine green (ICG) fluorescence in gastric reconstruction to determine a suitable anastomotic position during esophagectomy.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes 2020 (PRISMA) were followed for this analysis.

Results

A total of 9 publications including 1,162 patients were included. The operation time and intraoperative blood loss were comparable in the ICG and control groups. There was also no significant difference in overall postoperative mortality, reoperation, arrhythmia, vocal cord paralysis, pneumonia, and surgical wound infection. The ICG group had a 2.66-day reduction in postoperative stay. The overall anastomotic leak (AL) was 17.6% (n = 131) in the control group and 4.5% (n = 19) in the ICG group with a relative risk (RR) of 0.29 (95% CI 0.18–0.47). A subgroup analysis showed that the application of ICG in cervical anastomosis significantly reduced the incidence of AL (RR of 0.31, 95% CI 0.18–0.52), but for intrathoracic anastomosis, the RR 0.35 was not significant (95% CI 0.09–1.43). Compared to an RR of 0.35 in publications with a sample size of <50, a sample size of >50 had a lower RR of 0.24 (95% CI 0.12–0.48). Regarding intervention time of ICG, the application of ICG both before and after gastric construction had a better RR of 0.25 (95% CI 0.07–0.89).

Conclusions

The application of ICG fluorescence could effectively reduce the incidence of AL and shorten the postoperative hospital stay for patients undergoing cervical anastomosis but was not effective for patients undergoing intrathoracic anastomosis. The application of ICG fluorescence before and after gastric management can better prevent AL.

Systematic Review Registration

PROSPERO, CRD:42021244819.
Construction and Verification of Nomogram Model for Lung Adenocarcinoma With ≤ 5 Bone-Only Metastases Basing on Hematology Markers
Authors: Meng Chunliu , Wang Fang , Chen Minghong , Shi Hongyun , Zhao Lujun , Wang Ping
Published: June 2022

Objectives

This retrospective study investigated prognostic factors in advanced lung adenocarcinoma (LUAD) with one to five bone-only metastasis (BOM) and developed a nomogram model to estimate patient survival.

Methods

We investigated patients with advanced LUAD with one to five bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in two hospitals. A formula named Risk-H was constructed using hematological variables screened by LASSO-Cox regression analysis in the internal set and verified by the external set. Two nomogram models were developed by clinical variables selected by LASSO-Cox regression analysis with or without Risk-H in the internal set. The concordance index (C-index), calibration curves, time-dependent receiver operating characteristic (ROC) analysis, area under the curve (AUC), and decision curve analysis (DCA) were formulated to verify nomogram models. The primary endpoint was overall survival.

Results

We finally included 125 and 69 patients, respectively, in the internal and external sets for analysis. The following were significant hematology prognostic factors and were included in the Risk-H formula: alkaline phosphatase and albumin, leukocyte. Four clinical factors, including loss of weight, sensitive mutation status, T and N stage, with or without Risk-H were used to establish nomogram models. C-index, calibration curves, ROC analysis, AUC, and DCA showed the addition of hematological data improved the predictive accuracy of survival.

Conclusions

Pretreatment peripheral blood indexes may be a meaningful serum biomarker for prognosis in LUAD. The addition of Risk-H to the nomogram model could serve as a more economical, powerful, and practical method to predict survival for LUAD patients with one to five BOM.
The Role of Preoperative 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Retroperitoneal Sarcoma
Authors: Jo Sung Jun , Kim Kyeong Deok , Lim So Hee , Kim Jinseob , Hyun Seung Hyup , Park Jae Berm , Lee Kyo Won
Published: June 2022

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was used to predict pathologic grades based on the maximum standardized uptake value (SUVmax) in soft tissue sarcoma and bone sarcoma. In retroperitoneal sarcoma (RPS), the effectiveness of PET was not well known. This study was designed to investigate the association of SUVmax with histopathologic grade and evaluate the usefulness of 18F-FDG PET/CT before operation. Patients at Samsung Medical Center undergoing primary surgery for retroperitoneal sarcoma with preoperative 18F-FDG PET/CT imaging between January 2001 and February 2020 were investigated. The relationship between SUVmax and histologic features was assessed. The association of SUVmax with overall survival (OS), local recurrence (LR), and distant metastasis (DM) were studied. Of the total 129 patients, the most common histologic subtypes were liposarcoma (LPS; 68.2%) and leiomyosarcoma (LMS; 15.5%). The median SUVmax was 4.5 (range, 1- 29). Moreover, SUVmax was correlated with tumor grade (p < 0.001, Spearman coefficient; 0.627) and mitosis (p < 0.001, Spearman coefficient; 0.564) and showed a higher value in LMS (12.04 ± 6.73) than in dedifferentiated liposarcoma (DDLPS; 6.32 ± 4.97, p = 0.0054). SUVmax was correlated with pathologic parameters (tumor grade and mitosis) in RPS and was higher in the LMS group than the DDLPS group. The optimal SUVmax threshold to distinguish high tumor grade was 4.8. Those with a SUVmax greater than the threshold showed poor prognosis regarding OS, LR, and DM (p < 0.001).
Statin Treatment as a Targeted Therapy for APC-Mutated Colorectal Cancer
Authors: Shailes Hannah , Tse Wai Yiu , Freitas Marta O. , Silver Andrew , Martin Sarah A.
Published: June 2022

Background

Mutations in the tumor suppressor gene Adenomatous Polyposis Coli (APC) are found in 80% of sporadic colorectal cancer (CRC) tumors and are also responsible for the inherited form of CRC, Familial adenomatous polyposis (FAP).

Methods

To identify novel therapeutic strategies for the treatment of APC mutated CRC, we generated a drug screening platform that incorporates a human cellular model of APC mutant CRC using CRISPR-cas9 gene editing and performed an FDA-approved drug screen targeting over 1000 compounds.

Results

We have identified the group of HMG-CoA Reductase (HMGCR) inhibitors known as statins, which cause a significantly greater loss in cell viability in the APC mutated cell lines and in in vivo APC mutated patient derived xenograft (PDX) models, compared to wild-type APC cells. Mechanistically, our data reveals this new synthetic lethal relationship is a consequence of decreased Wnt signalling and, ultimately, a reduction in the level of expression of the anti-apoptotic protein Survivin, upon statin treatment in the APC-mutant cells only. This mechanism acts via a Rac1 mediated control of beta-catenin.

Conclusion

Significantly, we have identified a novel synthetic lethal dependence between APC mutations and statin treatment, which could potentially be exploited for the treatment of APC mutated cancers.
Comprehensive Analysis of the Function, Immune Profiles, and Clinical Implication of m1A Regulators in Lung Adenocarcinoma
Authors: Bao Guangyao , Li Tian , Guan Xiaojiao , Yao Yao , Liang Jie , Xiang Yifang , Zhong Xinwen
Published: June 2022

Background

Previous studies have demonstrated that transcriptional RNA methyladenosine modification significantly affects tumor initiation and progression. However, clinical implications of N1-methyladenosine (m1A) regulators and their effect on tumor immunity in lung adenocarcinoma (LUAD) are still poorly elucidated.

Methods

Herein, the characteristics of somatic mutation, copy number variation (CNV), DNA methylation, and expression levels of m1A regulators were thoroughly analyzed. We classified 955 lung adenocarcinoma patients into different m1A modification patterns based on an unsupervised consensus clustering algorithm. We then calculated the differences in gene expression, prognosis outcomes, and immune profiles among different m1A clusters. Subsequently, we screened differently expressed genes (DEGs) related to prognosis among different m1A clusters. We identified m1A related gene clusters according to the prognosis-related different expressed genes. We further constructed a scoring standard named the m1A score and comprehensively analyzed the survival outcomes, clinical-pathological features, immune microenvironment, treatment responses of immunotherapy, and drug susceptibility in different m1A score groups.

Results

In total, three different m1A modification patterns were identified, which contained cluster A, B, and C. Among them, cluster A processed the poorest clinical outcomes, the lowest immune cell infiltration rate, and the highest tumor purity score. Then, three m1A gene clusters (gene cluster A, B, C) were speculated. Subsequently, we combined m1A modification patterns and m1A gene cluster to classify lung adenocarcinoma patients into high and low m1A score groups. The low m1A score group was accompanied by higher mortality, higher tumor mutation burden (TMB) and genome mutation frequency, and lower programmed cell death-Ligand 1 (PD-L1) expression and tumor immune dysfunction and exclusion (TIDE) expression. Moreover, the m1A score exhibited positive correlation with almost all immune cells. Finally, common chemotherapeutic and targeted therapy agents exhibited obvious differences in drug susceptibility in different m1A score groups.

Conclusions

Collectively, we explored the potential value of m1A regulators in the prognosis and treatment of lung adenocarcinoma in multiple dimensions and provided some preliminary basis for the follow-up study of m1A regulators in lung adenocarcinoma.
Combining Clinicopathology, IVIM-DWI and Texture Parameters for a Nomogram to Predict Treatment Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients
Authors: Su Rixin , Wu Shusheng , Shen Hao , Chen Yaolin , Zhu Jingya , Zhang Yu , Jia Haodong , Li Mengge , Chen Wenju , He Yifu , Gao Fei
Published: June 2022

Objectives

This study aimed to create a nomogram for the risk prediction of neoadjuvant chemoradiotherapy (nCRT) resistance in locally advanced rectal cancer (LARC).

Methods

Clinical data in this retrospective study were collected from a total of 135 LARC patients admitted to our hospital from June 2016 to December 2020. After screening by inclusion and exclusion criteria, 62 patients were included in the study. Texture analysis (TA) was performed on T2WI and DWI images. Patients were divided into response group (CR+PR) and no-response group (SD+PD) according to efficacy assessment. Multivariate analysis was performed on clinicopathology, IVIM-DWI and texture parameters for screening of independent predictors. A nomogram was created and model fit and clinical net benefit were assessed.

Results

Multivariate analysis of clinicopathology parameters showed that the differentiation and T stage were independent predictors (OR values were 14.516 and 11.589, resp.; P<0.05). Multivariate analysis of IVIM-DWI and texture parameters showed that f value and Rads-score were independent predictors (OR values were 0.855, 2.790, resp.; P<0.05). In this study, clinicopathology together with IVIM-DWI and texture parameters showed the best predictive efficacy (AUC=0.979). The nomogram showed good predictive performance and stability in identifying high-risk LARC patients who are resistant to nCRT (C-index=0.979). Decision curve analyses showed that the nomogram had the best clinical net benefit. Ten-fold cross-validation results showed that the average AUC value was 0.967, and the average C-index was 0.966.

Conclusions

The nomogram combining the differentiation, T stage, f value and Rads-score can effectively estimate the risk of nCRT resistance in patients with LARC.