bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study of Relative Peripheral Refraction in Children With Different Degrees of Myopia
Authors: Xiaoli Lu , Xiangyue Zheng , Lihua Lian , Yuting Huang , Chuni Lin , Yujie Xia , Zhao Wang , Xiaoyi Yu
Published: March 2022

Purpose

To investigate the difference in the retinal refraction difference value (RDV) using multispectral refractive topography (MRT).

Methods

Ninety myopic participants, who met the enrolment requirements, were examined with an automatic optometer after mydriasis. According to the value of the spherical equivalent (SE), the participants were divided into Emmetropia group (E, +0.5D < SE < −0.5D), Low Myopia (LM, −0.5D < SE ≤ −3D), and Moderate and high Myopia (MM, −3D < SE ≤ −10D). The ocular biological parameters were detected by optical biometrics (Lenstar 900, Switzerland), including axial length (AL), lens thickness (LT), and keratometry (K1, K2). Furthermore, the MRT was used to measure the retinal RDV at three concentric areas, with 15-degree intervals from fovea into 45 degrees (RDV-15, RDV 15–30, and RDV 30–45), and four sectors, including RDV-S (RDV-Superior), RDV-I (RDV-Inferior), RDV-T (RDV-Temporal), and RDV-N (RDV-Nasal).

Results

In the range of RDV-15, there was a significant difference in the value of RDV-15 between Group E (−0.007 ± 0.148) vs. Group LM (−0.212 ± 0.399), and Group E vs. Group MM (0.019 ± 0.106) (P < 0.05); In the range of RDV 15–30, there was a significant difference in the value of RDV 15–30 between Group E (0.114 ± 0.219) vs. Group LM (−0.106 ± 0.332), and Group LM vs. Group MM (0.177 ± 0.209; P < 0.05); In the range of RDV 30–45, there was a significant difference in the value of RDV 30–45 between Group E (0.366 ± 0.339) vs. Group LM (0.461 ± 0.304), and Group E vs. Group MM (0.845 ± 0.415; P < 0.05); In the RDV-S position, there was a significant difference in the value of RDV-S between Group LM (−0.038 ± 0.636) and Group MM (0.526 ± 0.540) (P < 0.05); In the RDV-I position, there was a significant difference in the value of RDV-I between Group E (0.276 ± 0.530) vs. Group LM (0.594 ± 0.513), and Group E vs. Group MM (0.679 ± 0.589; P < 0.05). In the RDV-T position, there was no significant difference in the value of RDV-T among the three groups. In the RDV-N position, there was a significant difference in the value of RDV-N between Group E (0.352 ± 0.623) vs. Group LM (0.464 ± 0.724), and Group E vs. Group MM (1.078 ± 0.627; P < 0.05). The RDV analysis in all directions among the three groups showed a significant difference between RDV-S and RDV-I in Group LM (P < 0.05). Moreover, the correlation analysis showed that SE negatively correlated with AL, RDV 30–45, RDV-S, RDV-I, and RDV-N.

Conclusions

In this study, there was a significant difference in the value of RDV among Group E, Group LM, and Group MM, and the value of RDV in Group MM was the highest on the whole. In the range of RDV 30–45, there was a growing trend with the increase in the degree of myopia among the three groups. Furthermore, the SE negatively correlated with AL, RDV 30–45, RDV-S, RDV-I, and RDV-N.
Acute Exacerbation of Rheumatoid Arthritis Misdiagnosed as COVID-19: A Case Report
Authors: Torun Serife , Karaman Irem
Published: March 2022

Background

Rheumatoid arthritis (RA) is a systemic inflammatory connective tissue disease that affects 1–2% of the population worldwide. Pulmonary manifestations including interstitial lung disease (ILD), airway disease, pleural and vascular disease can be seen in up to 30–40% of patients with RA, which are recognized as the second most frequent cause of death in RA patients. The simultaneous occurrence of COVID-19 in RA patients with or without ILD, and the similarities and differences between RA-related ILD and COVID-19 lung findings have been reported in the literature. However, there was no reported case on differentiation of clinical findings of a patient with RA exacerbation causing a new diagnosis of ILD during the pandemic conditions.

Case Presentation

Here, we presented a patient with RA who was misdiagnosed as COVID-19 twice due to non-specific respiratory symptoms and ground-glass opacities observed in high-resolution CT. The misdiagnosis led to a delayed diagnosis of ILD and prolonged pulmonary symptoms.

Discussion

Clinicians must critically review patients throughout the diagnostic workup by thinking other diseases besides COVID-19, particularly in the absence of a confirmatory result. The link between ILD or ILD exacerbation and COVID-19 remains to be determined. While research continues in the field, it is important to consider the importance of COVID-19 in cases of ILD exacerbation, and vice versa.

Conclusion

Distinguishing lung imaging findings of COVID-19 from ILD is a major concern. Even though the primary manifestation of COVID-19 consists of respiratory symptoms, clinicians should be vigilant for other common conditions having the same symptoms. Clinicians should carefully distinguish a differential diagnosis between COVID-19 and a flare of rheumatic disease.
Deep Learning-Based Classification of Inflammatory Arthritis by Identification of Joint Shape Patterns—How Neural Networks Can Tell Us Where to “Deep Dive” Clinically
Authors: Folle Lukas , Simon David , Tascilar Koray , Krönke Gerhard , Liphardt Anna-Maria , Maier Andreas , Schett Georg , Kleyer Arnd
Published: March 2022

Objective:

We investigated whether a neural network based on the shape of joints can differentiate between rheumatoid arthritis (RA), psoriatic arthritis (PsA), and healthy controls (HC), which class patients with undifferentiated arthritis (UA) are assigned to, and whether this neural network is able to identify disease-specific regions in joints.

Methods

We trained a novel neural network on 3D articular bone shapes of hand joints of RA and PsA patients as well as HC. Bone shapes were created from high-resolution peripheral-computed-tomography (HR-pQCT) data of the second metacarpal bone head. Heat maps of critical spots were generated using GradCAM. After training, we fed shape patterns of UA into the neural network to classify them into RA, PsA, or HC.

Results

Hand bone shapes from 932 HR-pQCT scans of 617 patients were available. The network could differentiate the classes with an area-under-receiver-operator-curve of 82% for HC, 75% for RA, and 68% for PsA. Heat maps identified anatomical regions such as bare area or ligament attachments prone to erosions and bony spurs. When feeding UA data into the neural network, 86% were classified as “RA,” 11% as “PsA,” and 3% as “HC” based on the joint shape.

Conclusion

We investigated neural networks to differentiate the shape of joints of RA, PsA, and HC and extracted disease-specific characteristics as heat maps on 3D joint shapes that can be utilized in clinical routine examination using ultrasound. Finally, unspecific diseases such as UA could be grouped using the trained network based on joint shape.
Scorias spongiosa Polysaccharides Promote the Antioxidant and Anti-Inflammatory Capacity and Its Effect on Intestinal Microbiota in Mice
Authors: Xu Yingyin , Zhang Zhiyuan , Feng Huiyu , Tang Jie , Peng Weihong , Chen Ying , Zhou Jie , Wang Yong
Published: March 2022

Scorias spongiosa, as an edible fungus, has multiple health benefits. However, the effects of S. spongiosa on intestinal health are rarely explored. Hence, our study aims to elaborate on the influences of S. spongiosa polysaccharides (SSPs) on antioxidant, anti-inflammatory, and intestinal microflora in C57BL/6J mice. In the present study, 18 male mice were randomly distributed into three groups: (1) Control group (CON); (2) Low dose SSPs group (LSSP); (3) High dose SSPs group (HSSP). After 14-day administration, the jejunum and serum samples were collected for detection. The results showed that SSPs exert no effects on the growth performance of mice regardless of doses. Meanwhile, SSPs administration reduced the serum pro-inflammatory cytokines and elevated the anti-inflammatory cytokines. Moreover, the antioxidant capacity was elevated by SSPs administration, as evidenced by the increased contents of T-AOC, GSH-Px, and the decreased content of MDA. Mechanistically, the administration of SSPs enhanced the protein abundances of p-Nrf2, Keap1, and HO-1 in mice. The results of 16S rDNA demonstrated that the microbial community and composition were altered by SSPs administration. To summarize, SSPs benefit intestinal health in C57BL/6J mice via a mechanism that involves elevating antioxidant and anti-inflammatory activities and regulating intestinal microbiota.
Identification of circRNA Biomarker for Gastric Cancer through Integrated Analysis
Authors: Hossain Md. Tofazzal , Li Song , Reza Md. Selim , Feng Shengzhong , Zhang Xiaojing , Jin Zhe , Wei Yanjie , Peng Yin
Published: March 2022

Gastric cancer (GC) is one of the most common malignant tumors and ranks third in cancer mortality globally. Although, a lot of advancements have been made in diagnosis and treatment of gastric cancer, there is still lack of ideal biomarker for the diagnosis and treatment of gastric cancer. Due to the poor prognosis, the survival rate is not improved much. Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure that don’t have the 5′-3′ polarity and a 3′ polyA tail. Because of their circular structure, circRNAs are more stable than linear RNAs. Previous studies have found that circRNAs are involved in several biological processes like cell cycle, proliferation, apoptosis, autophagy, migration and invasion in different cancers, and participate in some molecular mechanisms including sponging microRNAs (miRNAs), protein translation and binding to RNA-binding proteins. Several studies have reported that circRNAs play crucial role in the occurrence and development of different types of cancers. Although, some studies have reported several circRNAs in gastric cancer, more studies are needed in searching new biomarkers for gastric cancer diagnosis and treatment. Here, we investigated potential circRNA biomarkers for GC using next-generation sequencing (NGS) data collected from 5 paired GC samples. A total of 45,783 circRNAs were identified in all samples and among them 478 were differentially expressed (DE). The gene ontology (GO) analysis of the host genes of the DE circRNAs showed that some genes were enriched in several important biological processes, molecular functions and cellular components. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that some host genes were enriched in several GC related pathways. The circRNA-miRNA-gene interaction network analysis showed that two circRNAs circCEACAM5 and circCOL1A1 were interacted with gastric cancer related miRNAs, and their host genes were also the important therapeutic and prognostic biomarkers for GC. The experimental results also validated that these two circRNAs were DE in GC compared to adjacent normal tissues. Overall, our findings suggest that these two circRNAs circCEACAM5 and circCOL1A1 might be the potential biomarkers for the diagnosis and treatment of GC.
Effect of 3-Month Aerobic Dance on Hippocampal Volume and Cognition in Elderly People With Amnestic Mild Cognitive Impairment: A Randomized Controlled Trial
Authors: Zhu Yi , Gao Yaxin , Guo Chuan , Qi Ming , Xiao Ming , Wu Han , Ma Jinhui , Zhong Qian , Ding Hongyuan , Zhou Qiumin , Ali Nawab , Zhou Li , Zhang Qin , Wu Ting , Wang Wei , Sun Cuiyun , Thabane Lehana , Zhang Ling , Wang Tong
Published: March 2022

As an intermediate state between normal aging and dementia, mild cognitive impairment (MCI), especially amnestic MCI (aMCI), is a key stage in the prevention and intervention of Alzheimer’s disease (AD). Whether dancing could increase the hippocampal volume of seniors with aMCI remains debatable. The aim of this study was to investigate the influence of aerobic dance on hippocampal volume and cognition after 3 months of aerobic dance in older adults with aMCI. In this randomized controlled trial, 68 elderly people with aMCI were randomized to either the aerobic dance group or the control group using a 1:1 allocation ratio. Ultimately, 62 of 68 participants completed this study, and the MRI data of 54 participants were included. A specially designed aerobic dance routine was performed by the dance group three times per week for 3 months, and all participants received monthly healthcare education after inclusion. MRI with a 3.0T MRI scanner and cognitive assessments were performed before and after intervention. High-resolution three-dimensional (3D) T1-weighted anatomical images were acquired for the analysis of hippocampal volume. A total of 35 participants (mean age: 71.51 ± 6.62 years) were randomized into the aerobic dance group and 33 participants (mean age: 69.82 ± 7.74 years) into the control group. A multiple linear regression model was used to detect the association between intervention and the difference of hippocampal volumes as well as the change of cognitive scores at baseline and after 3 months. The intervention group showed greater right hippocampal volume (β [95% CI]: 0.379 [0.117, 0.488], p = 0.002) and total hippocampal volume (β [95% CI]: 0.344 [0.082, 0.446], p = 0.005) compared to the control group. No significant association of age or gender was found with unilateral or global hippocampal volume. There was a correlation between episodic memory and intervention, as the intervention group showed a higher Wechsler Memory Scale-Revised Logical Memory (WMS-RLM) score (β [95% CI]: 0.326 [1.005, 6.773], p = 0.009). Furthermore, an increase in age may cause a decrease in the Mini-Mental State Examination (MMSE) score (β [95% CI]: −0.366 [−0.151, −0.034], p = 0.002). In conclusion, 3 months of aerobic dance could increase the right and total hippocampal volumes and improve episodic memory in elderly persons with aMCI.

Clinical Trial Registration: This study was registered on the Chinese Clinical Trial Registry [www.chictr.org.cn], identifier [ChiCTR-INR-15007420].
Real-Time Quaking- Induced Conversion Assays for Prion Diseases, Synucleinopathies, and Tauopathies
Authors: Vascellari Sarah , Orrù Christina D. , Caughey Byron
Published: March 2022

Prion diseases, synucleinopathies and tauopathies are neurodegenerative disorders characterized by deposition of abnormal protein aggregates in brain and other tissues. These aggregates consist of misfolded forms of prion, α-synuclein (αSyn), or tau proteins that cause neurodegeneration and represent hallmarks of these disorders. A main challenge in the management of these diseases is the accurate detection and differentiation of these abnormal proteins during the early stages of disease before the onset of severe clinical symptoms. Unfortunately, many clinical manifestations may occur only after neuronal damage is already advanced and definite diagnoses typically require post-mortem neuropathological analysis. Over the last decade, several methods have been developed to increase the sensitivity of prion detection with the aim of finding reliable assays for the accurate diagnosis of prion disorders. Among these, the real-time quaking-induced conversion (RT–QuIC) assay now provides a validated diagnostic tool for human patients, with positive results being accepted as an official criterion for a diagnosis of probable prion disease in multiple countries. In recent years, applications of this approach to the diagnosis of other prion-like disorders, such as synucleinopathies and tauopathies, have been developed. In this review, we summarize the current knowledge on the use of the RT-QuIC assays for human proteopathies.
Design, Implementation, and Evaluation of a Variable Stiffness Transradial Hand Prosthesis
Authors: Hocaoglu Elif , Patoglu Volkan
Published: March 2022

We present the design, implementation, and experimental evaluation of a low-cost, customizable, easy-to-use transradial hand prosthesis capable of adapting its compliance. Variable stiffness actuation (VSA) of the prosthesis is based on antagonistically arranged tendons coupled to nonlinear springs driven through a Bowden cable based power transmission. Bowden cable based antagonistic VSA can, not only regulate the stiffness and the position of the prosthetic hand but also enables a light-weight and low-cost design, by the opportunistic placement of motors, batteries, and controllers on any convenient location on the human body, while nonlinear springs are conveniently integrated inside the forearm. The transradial hand prosthesis also features tendon driven underactuated compliant fingers that allow natural adaption of the hand shape to wrap around a wide variety of object geometries, while the modulation of the stiffness of their drive tendons enables the prosthesis to perform various tasks with high dexterity. The compliant fingers of the prosthesis add inherent robustness and flexibility, even under impacts. The control of the variable stiffness transradial hand prosthesis is achieved by an sEMG based natural human-machine interface.
A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis
Authors: Weng Ze-An , Huang Xiao-Xiong , Deng Die , Yang Zhen-Guo , Li Shu-Yuan , Zang Jian-Kun , Li Yu-Feng , Liu Yan-Fang , Wu You-Sheng , Zhang Tian-Yuan , Su Xuan-Lin , Lu Dan , Xu An-Ding
Published: March 2022

Background

We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT).

Methods

A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA).

Results

After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842–0.933) and 0.776 (95% CI: 0.681–0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful.

Conclusions

The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.
Factors Associated With the Improvement of Left Ventricular Systolic Function by Continuous Positive Airway Pressure Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Obstructive Sleep Apnea
Authors: Naito Ryo , Kasai Takatoshi , Dohi Tomotaka , Takaya Hisashi , Narui Koji , Momomura Shin-ichi
Published: March 2022

Background

Obstructive sleep apnea (OSA) is a potential risk factor in cardiovascular diseases, including arrhythmia, coronary artery disease, and heart failure (HF). Continuous positive airway pressure (CPAP) therapy is an effective therapy for OSA and the underlying HF, partly through a 5–9% increase in the left ventricular ejection fraction (LVEF). However, the data on the factors associated with the efficacy of CPAP on LVEF in patients with HF complicated by OSA are scarce. This study aimed to investigate whether LVEF improves in patients with OSA and HF after 1 month of CPAP therapy, and to clarify which factors are associated with the degree of LVEF improvement.

Method

This was a prospective, single-arm, open-label study. We enrolled moderate-to-severe patients with OSA and HF who were being followed up at the cardiovascular center of Toranomon Hospital (Tokyo, Japan). The parameters of sleep study and LVEF were assessed at the baseline and after 1 month of CPAP. The multivariate regression analyses, with changes in LVEF as a dependent variable, were performed to determine the factors that were associated with the degree of LVEF improvement.

Results

We analyzed 55 consecutive patients with OSA and HF (mean age: 60.7 ± 12.2 years, mean LVEF value: 37.2 ± 9.8%). One month of CPAP treatment decreased the apnea-hypopnea index (AHI) from 45.3 ± 16.1 to 5.4 ± 4.1 per hour, and the LVEF improved from 37.2 ± 9.8 to 43.2 ± 11.7%. The multivariate regression analyses demonstrated that age and body mass index (BMI) were significant determinants of LVEF improvement.

Conclusion

The LVEF improved significantly after 1 month of CPAP therapy in Japanese patients with OSA and HF. Multivariate regression analyses indicated that an improvement in LVEF was likely to be observed in young patients with obesity.
Incidence and Long-Term Survival of Spontaneous Intracerebral Hemorrhage Over Time: A Systematic Review and Meta-Analysis
Authors: Li Xianqi , Zhang Li , Wolfe Charles D. A. , Wang Yanzhong
Published: March 2022

Background and Purpose

Recent epidemiological data indicate that the absolute number of hemorrhagic stroke cases increased by 47% between 1990 and 2010 and continued to cause high rates of death and disability. The last systematic review and meta-analysis of incidence and long-term survival of intracerebral hemorrhage (ICH) were published 11 and 7 years ago, respectively, and lacked comparison between different income groups, therefore, a more up to date analysis is needed. We aim to investigate the ICH incidence and long-term survival data in countries of different income groups.

Materials Methods

We systematically searched Ovid Medline for population-based longitudinal studies of first-ever spontaneous ICH published from January 2000 to December 2020. We performed meta-analyses on the incidence and survival rate in countries of 4 different income groups with random-effects models (severe inconsistency). The I2 was used to measure the heterogeneity. Heterogeneity was further investigated by conducting the meta-regression on the study mid-year. Time trends of the survival rate were assessed by weighted linear regression.

Results

We identified 84 eligible papers, including 68 publications reporting incidence and 24 publications on the survival rate. The pooled incidence of ICH per 100,000 per person-years was 26.47 (95% CI: 21.84–32.07) worldwide, 25.9 (95% CI: 22.63–29.63) in high-income countries (HIC), 28.45 (95% CI: 15.90–50.88) in upper-middle-income countries, and 31.73 (95% CI: 18.41–54.7) in lower-middle-income countries. The 1-year pooled survival rate was from 50% (95% CI: 47–54%; n = 4,380) worldwide to 50% (95% CI: 47–54%) in HIC, and 46% (95% CI: 38–55%) in upper-middle income countries. The 5-year pooled survival rate was 41% (95% CI: 35–48%; n = 864) worldwide, 41% (95% CI: 32–50%) in high-income and upper-middle countries. No publications were found reporting the long-term survival in lower-middle-income and low-income countries. No time trends in incidence or survival were found by meta-regression.

Conclusion

The pooled ICH incidence was highest in lower-middle-income countries. About half of ICH patients survived 1 year, and about two-fifths survived 5 years. Reliable population-based studies estimating the ICH incidence and long-term survival in low-income and low-middle-income countries are needed to help prevention of ICH.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=170140, PROSPERO CRD42020170140.
Effect of Obesity on Arithmetic Processing in Preteens With High and Low Math Skills: An Event-Related Potentials Study
Authors: Alatorre-Cruz Graciela C. , Downs Heather , Hagood Darcy , Sorensen Seth T. , Williams D. Keith , Larson-Prior Linda J.
Published: March 2022

Preadolescence is an important period for the consolidation of certain arithmetic facts, and the development of problem-solving strategies. Obese subjects seem to have poorer academic performance in math than their normal-weight peers, suggesting a negative effect of obesity on math skills in critical developmental periods. To test this hypothesis, event-related potentials (ERPs) were collected during a delayed-verification math task using simple addition and subtraction problems in obese [above 95th body mass index (BMI) percentile] and non-obese (between 5th and 90th BMI percentile) preteens with different levels of math skill; thirty-one with low math skills (14 obese, mean BMI = 26.40, 9.79 years old; 17 non-obese, BMI = 17.45, 9.76 years old) and thirty-one with high math skills (15 obese, BMI = 26.90, 9.60 years old; 16 non-obese, BMI = 17.13, 9.63 years old). No significant differences between weight groups were observed in task accuracy regardless of their mathematical skill level. For ERPs, electrophysiological differences were found only in the subtraction condition; participants with obesity showed an electrophysiologic pattern associated with a reduced ability to allocate attention resources regardless of their math skill level, these differences were characterized by longer P300 latency than their normal-weight peers. Moreover, the participants with obesity with high math skills displayed hypoactivity in left superior parietal lobule compared with their normal-weight peers. Additionally, obese preteens with low math skills displayed smaller arithmetic N400 amplitude than non-obese participants, reflecting difficulties in retrieving visual, semantic, and lexical information about numbers. We conclude that participants with obesity are less able than their normal-weight peers to deploy their attention regardless of their behavioral performance, which seems to have a greater effect on obese participants with low math skills because they also show problems in the retrieval of solutions from working memory, resulting in a delay in the development of mathematical skills.
Abnormality of Functional Connections in the Resting State Brains of Schizophrenics
Authors: Zhu Yan , Zhu Geng , Li Bin , Yang Yueqi , Zheng Xiaohan , Xu Qi , Li Xiaoou
Published: March 2022

To explore the change of brain connectivity in schizophrenics (SCZ), the resting-state EEG source functional connections of SCZ and healthy control (HC) were investigated in this paper. Different band single-layer networks, multilayer networks, and improved multilayer networks were constructed and their topological attributes were extracted. The topological attributes of SCZ and HC were automatically distinguished using ensemble learning methods called Ensemble Learning based on Trees and Soft voting method, and the effectiveness of different network construction methods was compared based on the classification accuracy. The results showed that the classification accuracy was 89.38% for α band network, 82.5% for multilayer network, and 86.88% for improved multilayer network. Comparing patients with SCZ to those with Alzheimer’s disease (AD), the classification accuracy of improved multilayer network was the highest, which was 88.12%. The power spectrum in the α band of SCZ was significantly lower than HC, whereas there was no significant difference between SCZ and AD. This indicated that the improved multilayer network can effectively distinguish SCZ and other groups not only when their power spectrum was significantly different. The results also suggested that the improved multilayer topological attributes were regarded as biological markers in the clinical diagnosis of patients with schizophrenia and even other mental disorders.
Quantitative Evaluation of the Association Between Fixation Stability and Phoria During Short-Term Binocular Viewing
Authors: Kim Sang-Yeob , Moon Byeong-Yeon , Cho Hyun Gug , Yu Dong-Sik
Published: March 2022

Purpose

Fixation stability for binocular anomalies with a phoria cannot be detected by direct observations. This study aimed to quantitatively evaluate fixation stability using an eye tracker rather than direct directions in binocular vision with abnormal and normal phorias.

Methods

Thirty-five and 25 participants with abnormal and normal phoria, respectively, were included in the study. The horizontal and vertical gaze points and convergence were recorded for 10 s using a remote eye tracker while binocularly viewing a target on a display screen 550 mm away. Fixation stability was quantified using bivariate contour ellipse areas (BCEA).

Results

The fixation stability for all participants-based evaluations as a single cluster in the abnormal phoria group was lower than that in the normal phoria group (p= 0.005). There was no difference between the two groups in the evaluation based on the BCEA for each participant-based evaluation (p= 0.66). Fixation stability was also more related to convergence for the abnormal phoria group than for the normal phoria group (r= 0.769,p< 0.001;r= 0.417,p= 0.038, respectively).

Conclusion

As the first study to evaluate fixation stability using an eye-tracker to differentiate between abnormal and normal phoria for non-strabismus, these findings may provide evidence for improving the evaluation of binocular vision not detected with clinical diagnostic tests.
Caveats and Nuances of Model-Based and Model-Free Representational Connectivity Analysis
Authors: Karimi-Rouzbahani Hamid , Woolgar Alexandra , Henson Richard , Nili Hamed
Published: March 2022

Brain connectivity analyses have conventionally relied on statistical relationship between one-dimensional summaries of activation in different brain areas. However, summarizing activation patterns within each area to a single dimension ignores the potential statistical dependencies between their multi-dimensional activity patterns. Representational Connectivity Analyses (RCA) is a method that quantifies the relationship between multi-dimensional patterns of activity without reducing the dimensionality of the data. We consider two variants of RCA. In model-free RCA, the goal is to quantify the shared information for two brain regions. In model-based RCA, one tests whether two regions have shared information about a specific aspect of the stimuli/task, as defined by a model. However, this is a new approach and the potential caveats of model-free and model-based RCA are still understudied. We first explain how model-based RCA detects connectivity through the lens of models, and then present three scenarios where model-based and model-free RCA give discrepant results. These conflicting results complicate the interpretation of functional connectivity. We highlight the challenges in three scenarios: complex intermediate models, common patterns across regions, and transformation of representational structure across brain regions. The article is accompanied by scripts (https://osf.io/3nxfa/) that reproduce the results. In each case, we suggest potential ways to mitigate the difficulties caused by inconsistent results. The results of this study shed light on some understudied aspects of RCA, and allow researchers to use the method more effectively.
EEG-fMRI: Ballistocardiogram Artifact Reduction by Surrogate Method for Improved Source Localization
Authors: Rusiniak Mateusz , Bornfleth Harald , Cho Jae-Hyun , Wolak Tomasz , Ille Nicole , Berg Patrick , Scherg Michael
Published: March 2022

For the analysis of simultaneous EEG-fMRI recordings, it is vital to use effective artifact removal tools. This applies in particular to the ballistocardiogram (BCG) artifact which is difficult to remove without distorting signals of interest related to brain activity. Here, we documented the use of surrogate source models to separate the artifact-related signals from brain signals with minimal distortion of the brain activity of interest. The artifact topographies used for surrogate separation were created automatically using principal components analysis (PCA-S) or by manual selection of artifact components utilizing independent components analysis (ICA-S). Using real resting-state data from 55 subjects superimposed with simulated auditory evoked potentials (AEP), both approaches were compared with three established BCG artifact removal methods: Blind Source Separation (BSS), Optimal Basis Set (OBS), and a mixture of both (OBS-ICA). Each method was evaluated for its applicability for ERP and source analysis using the following criteria: the number of events surviving artifact threshold scans, signal-to-noise ratio (SNR), error of source localization, and signal variance explained by the dipolar model. Using these criteria, PCA-S and ICA-S fared best overall, with highly significant differences to the established methods, especially in source localization. The PCA-S approach was also applied to a single subject Berger experiment performed in the MRI scanner. Overall, the removal of BCG artifacts by the surrogate methods provides a substantial improvement for the analysis of simultaneous EEG-fMRI data compared to the established methods.
The Application of Diffusion Kurtosis Imaging on the Heterogeneous White Matter in Relapsing-Remitting Multiple Sclerosis
Authors: Zhu Qiyuan , Zheng Qiao , Luo Dan , Peng Yuling , Yan Zichun , Wang Xiaohua , Chen Xiaoya , Li Yongmei
Published: March 2022

Objectives

To evaluate the microstructural damage in the heterogeneity of different white matter areas in relapsing-remitting multiple sclerosis (RRMS) patients by using diffusion kurtosis imaging (DKI) and its correlation with clinical and cognitive status.

Materials and Methods

Kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD) in T1-hypointense lesions (T1Ls), pure T2-hyperintense lesions (pure-T2Ls), normal-appearing white matter (NAWM), and white matter in healthy controls (WM in HCs) were measured in 48 RRMS patients and 26 sex- and age-matched HCs. All the participants were assessed with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Symbol Digit Modalities Test (SDMT) scores as the cognitive status. The Kurtzke Expanded Disability Status Scale (EDSS) scores were used to evaluate the clinical status in RRMS patients.

Results

The lowest KFA, FA, and MK values and the highest MD values were found in T1Ls, followed by pure-T2Ls, NAWM, and WM in HCs. The T1Ls and pure-T2Ls were significantly different in FA (p = 0.002) and MK (p = 0.013), while the NAWM and WM in HCs were significantly different in KFA, FA, and MK (p < 0.001; p < 0.001; p = 0.001). The KFA, FA, MK, and MD values in NAWM (r = 0.360, p = 0.014; r = 0.415, p = 0.004; r = 0.369, p = 0.012; r = −0.531, p < 0.001) were correlated with the MMSE scores and the FA, MK, and MD values in NAWM (r = 0.423, p = 0.003; r = 0.427, p = 0.003; r = −0.359, p = 0.014) were correlated with the SDMT scores.

Conclusion

Applying DKI to the imaging-based white matter classification has the potential to reflect the white matter damage and is correlated with cognitive impairment.
The Function of NF-Kappa B During Epilepsy, a Potential Therapeutic Target
Authors: Cai Mengtan , Lin Weihong
Published: March 2022

The transcriptional regulator nuclear factor kappa B (NF-κB) modulates cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. The NF-κB pathway plays a major role in the expressing genes related to inflammation, including chemokines, interleukins, and tumor necrosis factor. It also transcribes genes that can promote neuronal survival or apoptosis. Epilepsy is one of the most common brain disorders and it not only causes death worldwide but also affects the day-to-day life of affected individuals. While epilepsy has diverse treatment options, there remain patients who are not sensitive to the existing treatment methods. Recent studies have implicated the critical role of NF-κB in epilepsy. It is upregulated in neurons, glial cells, and endothelial cells, due to neuronal loss, glial cell proliferation, blood-brain barrier dysfunction, and hippocampal sclerosis through the glutamate and γ-aminobutyric acid imbalance, ion concentration changes, and other mechanisms. In this review, we summarize the functional changes caused by the upregulation of NF-κB in the central nervous system during different periods after seizures. This review is the first to deconvolute the complicated functions of NF-κB, and speculate that the regulation of NF-κB can be a safe and effective treatment strategy for epilepsy.
Improved Functional Organization in Patients With Primary Insomnia After Individually-Targeted Transcranial Magnetic Stimulation
Authors: Qi Shun , Zhang Yao , Li Xiang , Sun Chuanzhu , Ma Xiaowei , Li Sanzhong , Li Li , Ren Kai , Xi Min , Huang Zi-Gang
Published: March 2022

Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS.
The Link Between Obesity and the Skin
Authors: Darlenski Razvigor , Mihaylova Vesselina , Handjieva-Darlenska Teodora
Published: March 2022

Obesity as a multi-organ disease that affects the entire human organism. Notably, the skin is no exclusion from this postulate. Skin changes in obese patients have been widely studied with regards to mechanical friction, skin infections, and skin hypertrophic conditions, such as acanthosis nigricans and, most commonly, fibromas (skin tags). Almost 60–70% of obese patients present with a variety of skin changes. Herein, we discuss our own experience and review the complex skin changes in obesity. The role of metabolic syndrome and obesity are responsible for the epidemiological prevalence and are involved in the pathogenesis of chronic inflammatory skin diseases, such as psoriasis, atopic dermatitis, and skin malignancies. Here, we comment on the role of nutritional interventions in these patients as it has been proven that low-calorie diet and weight loss is related to improvement of inflammatory skin diseases. The readership of this paper will receive up-to-date overview on the connection between obesity and the skin that is of a practical importance to any clinician working in the field.
Optimized Conformal Total Body Irradiation methods with Helical TomoTherapy and Elekta VMAT: Implementation, Imaging, Planning and Dose Delivery for Pediatric Patients
Authors: Loginova Anna Anzorovna , Tovmasian Diana Anatolievna , Lisovskaya Anastasiya Olegovna , Kobyzeva Daria Alexeevna , Maschan Michael Alexandrovich , Chernyaev Alexander Petrovich , Egorov Oleg Borisovich , Nechesnyuk Alexey Vladimirovich
Published: March 2022

Optimized conformal total body irradiation (OC-TBI) is a highly conformal image guided method for irradiating the whole human body while sparing the selected organs at risk (OARs) (lungs, kidneys, lens). This study investigated the safety and feasibility of pediatric OC-TBI with the helical TomoTherapy (TomoTherapy) and volumetric modulated arc (VMAT) modalities and their implementation in routine clinical practice. This is the first study comparing the TomoTherapy and VMAT modalities in terms of treatment planning, dose delivery accuracy, and toxicity for OC-TBI in a single-center setting. The OC-TBI method with standardized dosimetric criteria was developed and implemented with TomoTherapy. The same OC-TBI approach was applied for VMAT. Standardized treatment steps, namely, positioning and immobilization, contouring, treatment planning strategy, plan evaluation, quality assurance, visualization and treatment delivery procedure were implemented for 157 patients treated with TomoTherapy and 52 patients treated with VMAT. Both modalities showed acceptable quality of the planned target volume dose coverage with simultaneous OARs sparing. The homogeneity of target irradiation was superior for TomoTherapy. Overall assessment of the OC-TBI dose delivery was performed for 30 patients treated with VMAT and 30 patients treated with TomoTherapy. The planned and delivered (sum of doses for all fractions) doses were compared for the two modalities in groups of patients with different heights. The near maximum dose values of the lungs and kidneys showed the most significant variation between the planned and delivered doses for both modalities. Differences in the patient size did not result in statistically significant differences for most of the investigated parameters in either the TomoTherapy or VMAT modality. TomoTherapy-based OC-TBI showed lower variations between planned and delivered doses, was less time-consuming and was easier to implement in routine practice than VMAT. We did not observe significant differences in acute and subacute toxicity between TomoTherapy and VMAT groups. The late toxicity from kidneys and lungs was not found during the 2.3 years follow up period. The study demonstrates that both modalities are feasible, safe and show acceptable toxicity. The standardized approaches allowed us to implement pediatric OC-TBI in routine clinical practice.
CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer
Authors: Qin Xiao-Ping , Lu Qi-Ji , Yang Cheng-Huizi , Wang Jue , Chen Jian-Fan , Liu Kan , Chen Xin , Zhou Jing , Pan Yu-Hang , Li Yong-Hong , Ren Shan-Cheng , Liu Jiu-Min , Liu Wei-Peng , Qian Hui-Jun , Yi Xian-Lin , Lai Cai-Yong , Qu Li-Jun , Gao Xin , Xu Yu-Sheng , Chen Zheng , Zhuo Yu-Min
Published: March 2022

Background

This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa.

Method

A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8.

Result

Multivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P<0.001; and OR: 1.43, 95% CI: 1.32-1.55, P<0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P<0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002).

Conclusion

A CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.
Pretreatment DCE-MRI-Based Deep Learning Outperforms Radiomics Analysis in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Peng Yunsong , Cheng Ziliang , Gong Chang , Zheng Chushan , Zhang Xiang , Wu Zhuo , Yang Yaping , Yang Xiaodong , Zheng Jian , Shen Jun
Published: March 2022

Purpose

To compare the performances of deep learning (DL) to radiomics analysis (RA) in predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) based on pretreatment dynamic contrast-enhanced MRI (DCE-MRI) in breast cancer.

Materials and Methods

This retrospective study included 356 breast cancer patients who underwent DCE-MRI before NAC and underwent surgery after NAC. Image features and kinetic parameters of tumors were derived from DCE-MRI. Molecular information was assessed based on immunohistochemistry results. The image-based RA and DL models were constructed by adding kinetic parameters or molecular information to image-only linear discriminant analysis (LDA) and convolutional neural network (CNN) models. The predictive performances of developed models were assessed by receiver operating characteristic (ROC) curve analysis and compared with the DeLong method.

Results

The overall pCR rate was 23.3% (83/356). The area under the ROC (AUROC) of the image-kinetic-molecular RA model was 0.781 [95% confidence interval (CI): 0.735, 0.828], which was higher than that of the image-kinetic RA model (0.629, 95% CI: 0.595, 0.663;P< 0.001) and comparable to that of the image-molecular RA model (0.755, 95% CI: 0.708, 0.802;P= 0.133). The AUROC of the image-kinetic-molecular DL model was 0.83 (95% CI: 0.816, 0.847), which was higher than that of the image-kinetic and image-molecular DL models (0.707, 95% CI: 0.654, 0.761; 0.79, 95% CI: 0.768, 0.812;P< 0.001) and higher than that of the image-kinetic-molecular RA model (0.778, 95% CI: 0.735, 0.828;P< 0.001).

Conclusions

The pretreatment DCE-MRI-based DL model is superior to the RA model in predicting pCR to NAC in breast cancer patients. The image-kinetic-molecular DL model has the best prediction performance.