bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Phenotypic Variability in Chinese Patients With Branchio-Oto-Renal or Branchio-Oto Syndrome
Authors: Feng Haifeng , Xu Hongen , Chen Bei , Sun Shuping , Zhai Rongqun , Zeng Beiping , Tang Wenxue , Lu Wei
Published: November 2021

Background: Branchio-oto-renal syndrome (BOR) and branchio-oto syndrome (BOS) are rare autosomal dominant disorders defined by varying combinations of branchial, otic, and renal anomalies. Here, we characterized the clinical features and genetic etiology of BOR/BOS in several Chinese families and then explored the genotypes and phenotypes of BOR/BOS-related genes, as well as the outcomes of auditory rehabilitation in different modalities.

Materials and Methods: Probands and all affected family members underwent detailed clinical examinations. Their DNA was subjected to whole-exome sequencing to explore the underlying molecular etiology of BOR/BOS; candidate variants were validated using Sanger sequencing and interpreted in accordance with the American College of Medical Genetics guidelines. In addition, a literature review concerning EYA1 and SIX1 alterations was performed to explore the genotypes and phenotypes of BOR/BOS-related genes.

Results: Genetic testing identified the novel deletion (c.1425delC, p(Asp476Thrfs*4); NM_000,503.6), a nonsense variant (c.889C > T, p(Arg297*)), and two splicing variants in the EYA1 gene (c.1050+1G > T and c.1140+1G > A); it also identified one novel missense variant in the SIX1 gene (c.316G > A, p(Val106Met); NM_005,982.4). All cases exhibited a degree of phenotypic variability between or within families. Middle ear surgeries for improving bone-conduction component hearing loss had unsuccessful outcomes; cochlear implantation (CI) contributed to hearing gains.

Conclusion: This is the first report of BOR/BOS caused by the SIX1 variant in China. Our findings increase the numbers of known EYA1 and SIX1 variants. They also emphasize the usefulness of genetic testing in the diagnosis and prevention of BOR/BOS while demonstrating that CI for auditory rehabilitation is a feasible option in some BOR/BOS patients.
Regulatory Effect of Resveratrol on Inflammation Induced by Lipopolysaccharides via Reprograming Intestinal Microbes and Ameliorating Serum Metabolism Profiles
Authors: Ding Sujuan , Jiang Hongmei , Fang Jun , Liu Gang
Published: November 2021

The purpose of this study was to explore the regulatory effect of resveratrol (RES) on lipopolysaccharide (LPS)-induced inflammation and its influence on intestinal microorganisms and serum atlas in murine models during the development of inflammation to explore a novel method for the regulation of inflammation. Mice were randomly assigned to three groups: control (CON), LPS, and RES–LPS. The results showed that RES mitigated the inflammatory damage to the intes-tines and liver induced by LPS. Compared with the LPS group, RES treatment decreased the levels of TNF-α, IL-6, IFN-γ, myeloperoxidase, and alanine aminotransferase in the liver. Serum metabolic profile monitoring showed that, compared with the CON group, LPS decreased the levels of five metabolites, including cycloartomunin and glycerol triundecanoate, and increased the levels of eight metabolites, including N-linoleoyl taurine and PE(O-16:0/20:5(5Z), 8Z, 11Z, 14Z, 17Z). Conversely, RES treatment increased the levels of eight metabolites, including pantothenic acid, homovanillic acid, and S-(formylmethyl)glutathione, and reduced seven metabolites, including lysoPE(20:4(8Z,11Z,14Z,17Z)/0:0) and 13-cis-retinoic acid, etc., in comparison with the LPS group. Moreover, RES treatment alleviated the negative effects of LPS on intestinal microbes by reducing, for instance, the relative abundance of Bacteroidetes and Alistipes, and increasing the relative abundance of Lactobacillus. These results suggest that RES has great potential for preventing in-flammation.
Localized Defect Detection from Spatially Mapped, In-Situ Process Data With Machine Learning
Authors: Halsey William , Rose Derek , Scime Luke , Dehoff Ryan , Paquit Vincent
Published: November 2021

In powder bed fusion additive manufacturing, machines are often equipped with in-situ sensors to monitor the build environment as well as machine actuators and subsystems. The data from these sensors offer rich information about the consistency of the fabrication process within a build and across builds. This information may be used for process monitoring and defect detection; however, little has been done to leverage this data from the machines for more than just coarse-grained process monitoring. In this work we demonstrate how these inherently temporal data may be mapped spatially by leveraging scan path information. We then train a XGBoost machine learning model to predict localized defects—specifically soot–using only the mapped process data of builds from a laser powder bed fusion process as input features. The XGBoost model offers a feature importance metric that will help to elucidate possible relationships between the process data and observed defects. Finally, we analyze the model performance spatially and rationalize areas of greater and lesser performance.
Case Report: Use of Liposomal Amphotericin B in Low Doses in Patients With Visceral Leishmaniasis
Authors: Ren Danfeng , Cao Wenya , Liu Xiaojing , Han Qunying , Fan Wanhu , Li Guoliang , Xia Han , Zhang Xi
Published: November 2021

Background: No consensus has been reached regarding the optimal therapy for visceral leishmaniasis (VL), which affects ~12 million people worldwide.

Case Presentation: This report described four cases of VL encountered in the First Affiliated Hospital of Xi'an Jiaotong University between October 2019 and December 2020. Of the four patients, one patient experienced relapse after antimonial treatment, and the remaining patients had primary VL (including one patient with impaired kidney function and one patient with hemophagocytic syndrome). All patients received a novel treatment protocol, namely the low-dose L-AmB therapy, which was characterized by a low initial dose, cautious dose escalation, and low-dose therapy as maintenance. All patients were cured without severe complications, and there was no further recurrence during follow-up.

Conclusions: This case series demonstrated the safety and efficacy of the low-dose L-AmB therapy for VL patients, providing novel treatment protocol for the VL.
Proportional Changes in Cognitive Subdomains During Normal Brain Aging
Authors: Statsenko Yauhen , Habuza Tetiana , Gorkom Klaus Neidl-Van , Zaki Nazar , Almansoori Taleb M. , Al Zahmi Fatmah , Ljubisavljevic Milos R. , Belghali Maroua
Published: November 2021

Background: Neuroscience lacks a reliable method of screening the early stages of dementia.

Objective: To improve the diagnostics of age-related cognitive functions by developing insight into the proportionality of age-related changes in cognitive subdomains.

Materials and Methods: We composed a battery of psychophysiological tests and collected an open-access psychophysiological outcomes of brain atrophy (POBA) dataset by testing individuals without dementia. To extend the utility of machine learning (ML) classification in cognitive studies, we proposed estimates of the disproportional changes in cognitive functions: an index of simple reaction time to decision-making time (ISD), ISD with the accuracy performance (ISDA), and an index of performance in simple and complex visual-motor reaction with account for accuracy (ISCA). Studying the distribution of the values of the indices over age allowed us to verify whether diverse cognitive functions decline equally throughout life or there is a divergence in age-related cognitive changes.

Results: Unsupervised ML clustering shows that the optimal number of homogeneous age groups is four. The sample is segregated into the following age-groups: Adolescents ∈ [0, 20), Young adults ∈ [20, 40), Midlife adults ∈ [40, 60) and Older adults ≥60 year of age. For ISD, ISDA, and ISCA values, only the median of the Adolescents group is different from that of the other three age-groups sharing a similar distribution pattern (p > 0.01). After neurodevelopment and maturation, the indices preserve almost constant values with a slight trend toward functional decline. The reaction to a moving object (RMO) test results (RMO_mean) follow another tendency. The Midlife adults group's median significantly differs from the remaining three age subsamples (p < 0.01). No general trend in age-related changes of this dependent variable is observed. For all the data (ISD, ISDA, ISCA, and RMO_mean), Levene's test reveals no significant changes of the variances in age-groups (p > 0.05). Homoscedasticity also supports our assumption about a linear dependency between the observed features and age.

Conclusion: In healthy brain aging, there are proportional age-related changes in the time estimates of information processing speed and inhibitory control in task switching. Future studies should test patients with dementia to determine whether the changes of the aforementioned indicators follow different patterns.
Computer-Delivered Cognitive Training and Transcranial Direct Current Stimulation in Patients With HIV-Associated Neurocognitive Disorder: A Randomized Trial
Authors: Ownby Raymond L. , Kim Jae
Published: November 2021

Objective: HIV infection is associated with impaired cognition, and as individuals grow older, they may also experience age-related changes in mental abilities. Previous studies have shown that computer-based cognitive training (CCT) and transcranial direct current stimulation (tDCS) may be useful in improving cognition in older persons. This study evaluated the acceptability of CCT and tDCS to older adults with HIV-associated neurocognitive disorder, and assessed their impact on reaction time, attention, and psychomotor speed.

Methods: In a single-blind randomized study, 46 individuals with HIV-associated mild neurocognitive disorder completed neuropsychological assessments and six 20-min training sessions to which they had been randomly assigned to one of the following conditions: (1) CCT with active tDCS; (2) CCT with sham tDCS, or (3) watching educational videos with sham tDCS. Immediately after training and again 1 month later, participants completed follow-up assessments. Outcomes were evaluated via repeated measures mixed effects models.

Results: Participant ratings of the intervention were positive. Effects on reaction time were not significant, but measures of attention and psychomotor speed suggested positive effects of the intervention.

Conclusion: Both CCT and tDCS were highly acceptable to older persons with HIV infection. CCT and tDCS may improve cognitive in affected individuals.

Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03440840].
Region-Specific Neurovascular Decoupling Associated With Cognitive Decline in Parkinson’s Disease
Authors: Shang Song’an , Zhang Hongying , Feng Yuan , Wu Jingtao , Dou Weiqiang , Chen Yu-Chen , Yin Xindao
Published: November 2021

Background: Cognitive deficits are prominent non-motor symptoms in Parkinson’s disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD.

Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups.

Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P < 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P < 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual–spatial performance (r = −0.36 and P = 0.014).

Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual–spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.
Localizing Epileptic Foci Using Simultaneous EEG-fMRI Recording: Template Component Cross-Correlation
Authors: Ebrahimzadeh Elias , Shams Mohammad , Seraji Masoud , Sadjadi Seyyed Mostafa , Rajabion Lila , Soltanian-Zadeh Hamid
Published: November 2021

Conventional EEG-fMRI methods have been proven to be of limited use in the sense that they cannot reveal the information existing in between the spikes. To resolve this issue, the current study obtains the epileptic components time series detected on EEG and uses them to fit the Generalized Linear Model (GLM), as a substitution for classical regressors. This approach allows for a more precise localization, and equally importantly, the prediction of the future behavior of the epileptic generators. The proposed method approaches the localization process in the component domain, rather than the electrode domain (EEG), and localizes the generators through investigating the spatial correlation between the candidate components and the spike template, as well as the medical records of the patient. To evaluate the contribution of EEG-fMRI and concordance between fMRI and EEG, this method was applied on the data of 30 patients with refractory epilepsy. The results demonstrated the significant numbers of 29 and 24 for concordance and contribution, respectively, which mark improvement as compared to the existing literature. This study also shows that while conventional methods often fail to properly localize the epileptogenic zones in deep brain structures, the proposed method can be of particular use. For further evaluation, the concordance level between IED-related BOLD clusters and Seizure Onset Zone (SOZ) has been quantitatively investigated by measuring the distance between IED/SOZ locations and the BOLD clusters in all patients. The results showed the superiority of the proposed method in delineating the spike-generating network compared to conventional EEG-fMRI approaches. In all, the proposed method goes beyond the conventional methods by breaking the dependency on spikes and using the outside-the-scanner spike templates and the selected components, achieving an accuracy of 97%. Doing so, this method contributes to improving the yield of EEG-fMRI and creates a more realistic perception of the neural behavior of epileptic generators which is almost without precedent in the literature.
MCSNet: Channel Synergy-Based Human-Exoskeleton Interface With Surface Electromyogram
Authors: Shi Kecheng , Huang Rui , Peng Zhinan , Mu Fengjun , Yang Xiao
Published: November 2021

The human–robot interface (HRI) based on biological signals can realize the natural interaction between human and robot. It has been widely used in exoskeleton robots recently to help predict the wearer's movement. Surface electromyography (sEMG)-based HRI has mature applications on the exoskeleton. However, the sEMG signals of paraplegic patients' lower limbs are weak, which means that most HRI based on lower limb sEMG signals cannot be applied to the exoskeleton. Few studies have explored the possibility of using upper limb sEMG signals to predict lower limb movement. In addition, most HRIs do not consider the contribution and synergy of sEMG signal channels. This paper proposes a human–exoskeleton interface based on upper limb sEMG signals to predict lower limb movements of paraplegic patients. The interface constructs an channel synergy-based network (MCSNet) to extract the contribution and synergy of different feature channels. An sEMG data acquisition experiment is designed to verify the effectiveness of MCSNet. The experimental results show that our method has a good movement prediction performance in both within-subject and cross-subject situations, reaching an accuracy of 94.51 and 80.75%, respectively. Furthermore, feature visualization and model ablation analysis show that the features extracted by MCSNet are physiologically interpretable.
Adaptive Immune Deficiency Impairs Neural Activity After Training and Retrieval
Authors: Li Huiping , Fu Zhongxiao , Hu Meixin , Xu Xiu
Published: November 2021

Neuroimmune interactions have been studied for decades. Several neurodevelopmental disorders have been associated with immune dysfunction. However, the effects of immune system on neuronal function remain unknown. Herein, based on c-Fos protein expression, we characterized the brain areas that are activated after contextual fear conditioning (CFC) training or retrieval in severe combined immune deficiency (SCID) and wild-type mice. Further, we analyzed the interregional correlations of c-Fos activity that are affected by deficiency in adaptive immunity. Results showed significantly lower c-Fos density in learning and memory-associated brain regions of SCID mice after memory retrieval, but not during the CFC training. Moreover, SCID mice exhibited remarkably discordant interregional neuronal activities of learning neuron circuits after CFC training, which could be the cause of inefficient activation of the memory circuit after retrieval. These results provide a new perspective on how adaptive immunity affects neuronal function. Adaptive immune deficiency impairs the coordination of neural activity after training and retrieval, which might be a potential therapeutic target for neurodevelopmental disorders.
The Correlation Between Hearing Loss, Especially High-Frequency Hearing Loss and Cognitive Decline Among the Elderly
Authors: Diao Tongxiang , Ma Xin , Zhang Junbo , Duan Maoli , Yu Lisheng
Published: November 2021

Objective: The relation between cognition and hearing loss has been increasingly paid high attention, however, few studies have focused on the role of high-frequency hearing loss in cognitive decline. This study is oriented to role of hearing loss especially high-frequency hearing loss in cognitive impairment among elderly people (age ≥ 60 years).

Methods: The Montreal Cognitive Assessment Scale (MoCA) and pure tone audiometry were used to investigate the hearing loss and cognitive function of 201 elderly people older than 60 years. Factors possibly related to cognitive impairment including age, years of education, occupation, living conditions, history of otologic diseases, and high blood pressure were registered. This study consisted of two parts. First, univariate analysis and multiple linear regressions were performed to analyze the possible influencing factors of cognitive function among the 201 elderly people. Second, average hearing thresholds of low frequencies (250, 500 Hz), intermediate frequencies (1 k, 2 kHz), and high frequencies (4 k, 8 kHz) were calculated to screen out 40 cases with high-frequency hearing loss alone and 18 cases with normal hearing. Univariate analysis was used to compare the general condition, cognitive function, and each cognitive domain between the two groups, analyzing the relation between high-frequency hearing loss and cognitive function.

Result: We found that age, years of education, pure tone average (PTA), occupation, living condition, history of otologic diseases, years of self-reported hearing loss, and hypertension history were related to cognitive function. Furthermore, age, education experience, duration of self-reported hearing loss, and hypertension were independent factors (p < 0.05). PTA was negatively related with attention, orientation, and general cognition (p < 0.05). There were only 18 cases (9.0%) with normal hearing, and 40 cases (19.9%) with abnormal high-frequency hearing alone. The overall cognitive function showed no significant difference between them (p > 0.05); in contrast, the speech and abstract ability were significantly decreased in cases with high-frequency hearing loss (p < 0.05).

Conclusion: The increase of PTA among the elderly may affect the overall cognition by reducing attention and orientation. High-frequency hearing loss alone can affect the language and abstract ability to a certain extent, which is worthy of more attention.
Secondary Malnutrition and Nutritional Intervention in Cholestatic Liver Diseases in Infants
Authors: Larrosa-Haro Alfredo , Caro-Sabido Erika A.
Published: November 2021

We aimed to conduct an updated review on the pathophysiology, diagnosis, and nutritional intervention of CCLD and secondary malnutrition in infants. Protein-energy malnutrition, impaired linear growth, fat-soluble vitamin deficiencies, and hepatic osteodystrophy can occur in up to 80% of cases. The proposed pathophysiological mechanisms include insufficient energy intake, lipid- and fat-soluble vitamin malabsorption, increased energy expenditure, altered intermediate metabolism, hormonal dysregulation, and systemic inflammation. The current approach to diagnosis is the identification of the deviation of growth parameters, body composition, and serum concentration of micronutrients, which determines the type and magnitude of malnutrition. Currently, liver transplantation is the best therapeutic alternative for the reversal of nutritional impairment. Early and effective portoenteroanatomosis can extend survival in patients with biliary atresia. Medical and dietary interventions in some storage and metabolic diseases can improve liver damage and thus the nutritional status. A proportion of patients with biliary atresia have fat-soluble vitamin deficiencies despite receiving these vitamins in a water-soluble form. With aggressive enteral nutrition, it may be possible to increase fat stores and preserve muscle mass and growth. The nutritional issues identified in the pre- and post-transplantation stages include muscle mass loss, bone demineralization, growth retardation, and obesity, which seems to correspond to the natural history of CCLD. Due to the implications for the growth and development of infants with CCLD with this complex malnutrition syndrome, innovative projects are required, such as the generation of prediction and risk models, biomarkers of growth and body composition, and effective strategies for nutritional prevention and intervention.
The Double Burden of Malnutrition at the Individual Level Among Adults: A Nationwide Survey in the Philippines
Authors: de Juras Aileen R. , Hsu Wan-Chen , Hu Susan C.
Published: November 2021

Introduction: Double burden of malnutrition (DBM) is a fast-evolving public health challenge. The rising prevalence of obesity and diet-related non-communicable diseases alongside persistent nutritional deficiencies are compelling problems in many developing countries. However, there is limited evidence on the coexistence of these conditions in the same individual among community-dwelling adults. This cross-sectional study describes the various forms of DBM and examines the determinants of DBM at the individual level among adults in the Philippines.

Materials and Methods: A nationwide dataset from the 2013 Philippine National Nutrition Survey was used. The final study sample consisted of 17,157 adults (8,596 men and 8,561 non-pregnant and non-lactating women). This study focused on three DBM types within adults: (#1) Underweight and at least one cardiometabolic risk factor (Uw + ≥1 CMRF), (#2) Anemia and at least one cardiometabolic risk factor (An + ≥1 CMRF), (#3) Vitamin A deficiency or iodine insufficiency and at least one cardiometabolic risk factor (Other MND + ≥1 CMRF). The total double burden of malnutrition was also evaluated as the sum of the aforementioned three types. Logistic regression models were used to assess associations between socio-demographic and lifestyle factors and DBM.

Results: The prevalence of the three types of DBM were: type #1, 8.1%; type #2, 5.6%; type #3, 20.6%, and the total DBM prevalence was 29.4%. Sex, age, educational attainment, employment status, wealth quintile, and alcohol drinking were the risk factors for DBM. In contrast, marital status, smoking, and physical activity were associated with the different DBM types.

Conclusion: The study findings contribute to the current state of knowledge on the broad spectrum of individual-level DBM. Understanding the disparities of this phenomenon could guide integrated actions directed to the concomitance of malnutrition in various forms and cardiometabolic disease risks.
B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
Authors: Long Cheng , Li Gaowei , Zhang Chengyun , Jiang Tao , Li Yanjun , Duan Xin , Zhong Gang
Published: November 2021

Objective

chordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas.

Methods

we profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro.

Results

We found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion.

Conclusions

Our results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.
Development and Validation of an MRI-Based Nomogram Model for Predicting Disease-Free Survival in Locally Advanced Rectal Cancer Treated With Neoadjuvant Radiotherapy
Authors: Chen Silin , Tang Yuan , Li Ning , Jiang Jun , Jiang Liming , Chen Bo , Fang Hui , Qi Shunan , Hao Jing , Lu Ningning , Wang Shulian , Song Yongwen , Liu Yueping , Li Yexiong , Jin Jing
Published: November 2021

Objectives

To develop a prognostic prediction MRI-based nomogram model for locally advanced rectal cancer (LARC) treated with neoadjuvant therapy.

Methods

This was a retrospective analysis of 233 LARC (MRI-T stage 3-4 (mrT) and/or MRI-N stage 1-2 (mrN), M0) patients who had undergone neoadjuvant radiotherapy and total mesorectal excision (TME) surgery with baseline MRI and operative pathology assessments at our institution from March 2015 to March 2018. The patients were sequentially allocated to training and validation cohorts at a ratio of 4:3 based on the image examination date. A nomogram model was developed based on the univariate logistic regression analysis and multivariable Cox regression analysis results of the training cohort for disease-free survival (DFS). To evaluate the clinical usefulness of the nomogram, Harrell’s concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were conducted in both cohorts.

Results

The median follow-up times were 43.2 months (13.3–61.3 months) and 32.0 months (12.3–39.5 months) in the training and validation cohorts. Multivariate Cox regression analysis identified MRI-detected extramural vascular invasion (mrEMVI), pathological T stage (ypT) and perineural invasion (PNI) as independent predictors. Lymphovascular invasion (LVI) (which almost reached statistical significance in multivariate regression analysis) and three other independent predictors were included in the nomogram model. The nomogram showed the best predictive ability for DFS (C-index: 0.769 (training cohort) and 0.776 (validation cohort)). It had a good 3-year DFS predictive capacity [area under the curve, AUC=0.843 (training cohort) and 0.771 (validation cohort)]. DCA revealed that the use of the nomogram model was associated with benefits for the prediction of 3-year DFS in both cohorts.

Conclusion

We developed and validated a novel nomogram model based on MRI factors and pathological factors for predicting DFS in LARC treated with neoadjuvant therapy. This model has good predictive value for prognosis, which could improve the risk stratification and individual treatment of LARC patients.
Pathogenic in-Frame Variants in SCN8A: Expanding the Genetic Landscape of SCN8A-Associated Disease
Authors: Wong Jennifer C. , Butler Kameryn M. , Shapiro Lindsey , Thelin Jacquelyn T. , Mattison Kari A. , Garber Kathryn B. , Goldenberg Paula C. , Kubendran Shobana , Schaefer G. Bradley , Escayg Andrew
Published: November 2021

Numerous SCN8A mutations have been identified, of which, the majority are de novo missense variants. Most mutations result in epileptic encephalopathy; however, some are associated with less severe phenotypes. Mouse models generated by knock-in of human missense SCN8A mutations exhibit seizures and a range of behavioral abnormalities. To date, there are only a few Scn8a mouse models with in-frame deletions or insertions, and notably, none of these mouse lines exhibit increased seizure susceptibility. In the current study, we report the generation and characterization of two Scn8a mouse models (ΔIRL/+ and ΔVIR/+) carrying overlapping in-frame deletions within the voltage sensor of domain 4 (DIVS4). Both mouse lines show increased seizure susceptibility and infrequent spontaneous seizures. We also describe two unrelated patients with the same in-frame SCN8A deletion in the DIV S5-S6 pore region, highlighting the clinical relevance of this class of mutations.
A Series Solution for 2D Scattering of Cylindrical SH-Waves by Surrounding Loose Rock Zone of Underground Tunnel Lining
Authors: Jin Liguo , Sun Hongyang , Wang Shengnian , Zhou Zhenghua
Published: November 2021

This paper presents a closed-form series solution of cylindrical SH-wave scattering by the surrounding loose rock zone of underground tunnel lining in a uniform half-space based on the wave function expansion method and the mirror image method. The correctness of the series solution is verified through residual convergence and comparison with the published results. The influence of the frequency of the incident cylindrical SH-wave, the distance between the wave source and the lining, the lining buried depth, and the properties of the surrounding loose rock zone on the dynamic stress concentration of the tunnel lining is investigated. The results show that the incident wave with high frequency always makes the dynamic stress concentration of the tunnel lining obvious. With the increase of the distance between the wave source and the tunnel lining, the stress around the tunnel lining decreases, but the dynamic stress concentration factor around the tunnel lining does not decrease significantly but occasionally increases. The ground surface has a great influence on the stress concentration of the tunnel lining. The amplitude of the stress concentration factor of tunnel lining is highly related to the shear wave velocity of the surrounding loose rock zone. When the property of the surrounding rock (shear wave velocity) changes more, the amplitude of the stress concentration factor is larger, that is, the stress concentration is more significant.
Moderate Intensity Aerobic Exercise Potential Favorable Effect Against COVID-19: The Role of Renin-Angiotensin System and Immunomodulatory Effects
Authors: Arazi Hamid , Falahati Akram , Suzuki Katsuhiko
Published: November 2021

The coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the angiotensin converting enzyme 2 (ACE2) is the cellular receptor of SARS-CoV-2, it has a strong interaction with the renin angiotensin system (RAS). Experimental studies have shown that the higher levels of ACE2 or increasing ACE2/ACE1 ratio improve COVID-19 outcomes through lowering inflammation and death. Aerobic moderate intensity physical exercise fights off infections by two mechanisms, the inhibition of ACE/Ang II/AT1-R pathway and the stimulation of ACE2/Ang-(1–7)/MasR axis. Exercise can also activate the anti-inflammatory response so that it can be a potential therapeutic strategy against COVID-19. Here, we summarize and focus the relation among COVID-19, RAS, and immune system and describe the potential effect of aerobic moderate intensity physical exercise against CoV as a useful complementary tool for providing immune protection against SARS-CoV-2 virus infection, which is a novel intervention that requires further investigation.
Spacing, Feedback, and Testing Boost Vocabulary Learning in a Web Application
Authors: Belardi Angelo , Pedrett Salome , Rothen Nicolas , Reber Thomas P.
Published: November 2021

Information and communication technology (ICT) becomes more prevalent in education but its general efficacy and that of specific learning applications are not fully established yet. One way to further improve learning applications could be to use insights from fundamental memory research. We here assess whether four established learning principles (spacing, corrective feedback, testing, and multimodality) can be translated into an applied ICT context to facilitate vocabulary learning in a self-developed web application. Effects on the amount of newly learned vocabulary were assessed in a mixed factorial design (3×2×2×2) with the independent variables Spacing (between-subjects; one, two, or four sessions), Feedback (within-subjects; with or without), Testing (within-subjects, 70 or 30% retrieval trials), and Multimodality (within-subjects; unimodal or multimodal). Data from 79 participants revealed significant main effects for Spacing [F(2,76) = 8.51,p= 0.0005,ηp2=0.18] and Feedback [F(1,76) = 21.38,p< 0.0001,ηp2=0.22], and a significant interaction between Feedback and Testing [F(1,76) = 14.12,p= 0.0003,ηp2=0.16]. Optimal Spacing and the presence of corrective Feedback in combination with Testing together boost learning by 29% as compared to non-optimal realizations (massed learning, testing with the lack of corrective feedback). Our findings indicate that established learning principles derived from basic memory research can successfully be implemented in web applications to optimize vocabulary learning.
Falling in Love With Work: The Effect of Enterprise Social Media on Thriving at Work
Authors: Liu DongXu , Hou Beigang , Liu Yuanyuan , Liu Pingqing
Published: November 2021

Using a survey of 300 employees in different types of enterprises and different positions, this study verified that the use of enterprise social media has a positive effect on employees’ work exuberance. The study separately examined the effects of social media applications for work tasks and social tasks. Both types of applications had a positive impact on employees’ work exuberance. The study also identified the mediating role of challenge and obstructive stressors in this relationship. Work-related social media applications enhanced employees’ exuberance by reducing obstructive stressors, and social-related social media applications enhanced employees’ exuberance by reducing challenge stressors. The implications of these findings are that managers should pay attention to the use of enterprise social media, especially for social tasks, as this can enhance employees’ sense of exuberance.
The Deficits of Individual Morphological Covariance Network Architecture in Schizophrenia Patients With and Without Violence
Authors: Shen Danlin , Li Qing , Liu Jianmei , Liao Yi , Li Yuanyuan , Gong Qiyong , Huang Xiaoqi , Li Tao , Li Jing , Qiu Changjian , Hu Junmei
Published: November 2021

Background: Schizophrenia is associated with a significant increase in the risk of violence, which constitutes a public health concern and contributes to stigma associated with mental illness. Although previous studies revealed structural and functional abnormalities in individuals with violent schizophrenia (VSZ), the neural basis of psychotic violence remains controversial.

Methods: In this study, high-resolution structural magnetic resonance imaging (MRI) data were acquired from 18 individuals with VSZ, 23 individuals with non-VSZ (NSZ), and 22 age- and sex-matched healthy controls (HCs). Whole-brain voxel-based morphology and individual morphological covariance networks were analysed to reveal differences in gray matter volume (GMV) and individual morphological covariance network topology. Relationships among abnormal GMV, network topology, and clinical assessments were examined using correlation analyses.

Results: GMV in the hypothalamus gradually decreased from HCs and NSZ to VSZ and showed significant differences between all pairs of groups. Graph theory analyses revealed that morphological covariance networks of HCs, NSZ, and VSZ exhibited small worldness. Significant differences in network topology measures, including global efficiency, shortest path length, and nodal degree, were found. Furthermore, changes in GMV and network topology were closely related to clinical performance in the NSZ and VSZ groups.

Conclusions: These findings revealed the important role of local structural abnormalities of the hypothalamus and global network topological impairments in the neuropathology of NSZ and VSZ, providing new insight into the neural basis of and markers for VSZ and NSZ to facilitate future accurate clinical diagnosis and targeted treatment.
China's Hainan Free Trade Port: Medical Laws and Policy Reform
Authors: Qi Fei , Wu Yuqi , Wang Jing , Wang Qi
Published: November 2021

In 2018, the government of China decided to develop Hainan Province as the country's first free trade port operating within the country's socialist system. Based on this strategy, Hainan reformed its medical laws and policies to make it freer and more open. For example, Hainan formulated policies for more rapid and convenient access of foreign medicine and sanitary equipment (MSE), allowed manufacturers to register MSE in China with real-world data (RWD), and provided legal and visa conveniences for international medical teams to carry out various activities, including: diagnosis, treatment and scientific research. Hainan's reforms are not only conducive to the improvement of local medical and public health levels, but also provide opportunities for international MSE manufacturers and medical research institutions swiftly to enter China's huge medical market. However, with opportunity comes risk: Hainan should be on guard against public health risks associated with medical tourism, and decide how to strike a reasonable balance between protecting local MSE enterprises and improving the accessibility of imported MSE through policies and legislation. Finally, the paper recommends that Hainan should improve the regulatory system as soon as possible to ensure the quality of diagnosis and treatment in its new hospitals, and deal with data and information security risks in the RWD research.
Development of a New Temporary Attachment Technique for Detecting Debonding of a Composite Structure Using Impedance Based Non-Destructive Testing Method
Authors: Seo Dong-Woo , Jung Kyu-San , Kim Yi-Seul , Kim Hyung-Jin , Na Wongi S.
Published: November 2021

To date, the application of composite materials has been used throughout the globe due to its advantages, such as corrosion resistance, high strength, design flexibility, and light weight. However, the joining of composite materials is usually achieved with adhesives, where debonding of parts can cause unexpected failure. Thus, detecting and locating defects due to impact or fatigue stresses at an early stage is crucial to ensure safety. Various non-destructive testing (NDT) techniques have been used to detect defects in composite structures, where this study proposes an improved approach of using one of the NDT techniques to detect and locate debonding of glass fiber epoxy plates. Here, the electromechanical impedance (EMI) technique is used with a new way of detecting defects using a movable device. This idea could reduce the overall cost of the monitoring system as the conventional EMI technique requires one to permanently attach a large number of piezoelectric transducers when monitoring large structures. The performance of the proposed idea is tested against another temporary attachment method to investigate the possibility of using the new idea for monitoring debonding in composite structures.
The Effect of Rivaroxaban on CYP4F2 and Transcription Factors’ Activity in HUVECs
Authors: Ciapiene Ieva , Tatarunas Vacis , Giedraitiene Agne , Zvikas Vaidotas , Jakstas Valdas , Veikutiene Audrone , Meskauskaite Ugne , Venckyte Ugne , Pukalskas Audrius , Lesauskaite Vaiva
Published: November 2021

Interindividual variabilities between patients taking the anticoagulant rivaroxaban are a result of hepatic metabolism by CYP 450 enzymes. The objective of this study was to evaluate the impact of rivaroxaban on CYP4F2 and transcription factors’ activity in HUVECs. Rivaroxaban and its metabolites were detected by UPLC-ESI-MS and UPLC-QTOF-MS. CYP4F2, HNF4α, PXR and CAR expressions were determined in HUVECs by qPCR; CYP4F2 protein concentration was determined by ELISA. Rivaroxaban metabolites (M-1, M-2, M-5, M-8, M-10, M-11 and M-18) were detected in endothelial cells’ culture medium. Increasing concentrations of rivaroxaban determined lower 13-docosenamide concentrations. Rivaroxaban and dexamethasone reduced the expression of CYP4F2 when hsa-miR-24-3p—both CYP4F2 expression and CYP4F2 protein levels in HUVECs. The expression of the transcription factors HNF4α, PXR and CAR was not detected in HUVECs.
Forecasting the Daily Maximal and Minimal Temperatures from Radiosonde Measurements Using Neural Networks
Authors: Skok Gregor , Hoxha Doruntina , Zaplotnik Žiga
Published: November 2021

This study investigates the potential of direct prediction of daily extremes of temperature at 2 m from a vertical profile measurement using neural networks (NNs). The analysis is based on 3800 daily profiles measured in the period 2004–2019. Various setups of dense sequential NNs are trained to predict the daily extremes at different lead times ranging from 0 to 500 days into the future. The short- to medium-range forecasts rely mainly on the profile data from the lowest layer—mostly on the temperature in the lowest 1 km. For the long-range forecasts (e.g., 100 days), the NN relies on the data from the whole troposphere. The error increases with forecast lead time, but at the same time, it exhibits periodic behavior for long lead times. The NN forecast beats the persistence forecast but becomes worse than the climatological forecast on day two or three. The forecast slightly improves when the previous-day measurements of temperature extremes are added as a predictor. The best forecast is obtained when the climatological value is added as well, with the biggest improvement in the long-term range where the error is constrained to the climatological forecast error.
DNA Dosimetry with Gold Nanoparticle Irradiated by Proton Beams: A Monte Carlo Study on Dose Enhancement
Authors: Huynh Ngoc Han , Chow James C. L.
Published: November 2021

Heavy atom nanoparticles, such as gold nanoparticles, are proven effective radiosensitizers in radiotherapy to enhance the dose delivery for cancer treatment. This study investigated the effectiveness of cancer cell killing, involving gold nanoparticle in proton radiation, by changing the nanoparticle size, proton beam energy, and distance between the nanoparticle and DNA. Monte Carlo (MC) simulation (Geant4-DNA code) was used to determine the dose enhancement in terms of dose enhancement ratio (DER), when a gold nanoparticle is present with the DNA. With varying nanoparticle size (radius = 15–50 nm), distance between the gold nanoparticle and DNA (30–130 nm), as well as proton beam energy (0.5–25 MeV) based on the simulation model, our results showed that the DER value increases with a decrease of distance between the gold nanoparticle and DNA and a decrease of proton beam energy. The maximum DER (1.83) is achieved with a 25 nm-radius gold nanoparticle, irradiated by a 0.5 MeV proton beam and 30 nm away from the DNA.
Studies on Multi-Constraints Cooperative Guidance Method Based on Distributed MPC for Multi-Missiles
Authors: Cong Mingyu , Cheng Xianghong , Zhao Zhiquan , Li Zhijun
Published: November 2021

Cooperative terminal guidance with impact angle constraint is a key technology to achieve a saturation attack and improve combat effectiveness. The present study envisaged cooperative terminal guidance with impact angle constraint for multiple missiles. In this pursuit, initially, the three-dimensional cooperative terminal guidance law with multiple constraints was studied. The impact time cooperative strategy of virtual leader missile and follower missiles was designed by introducing virtual leader missiles. Subsequently, based on the distributed model prediction control combined with the particle swarm optimization algorithm, a cooperative terminal guidance algorithm was designed for multiple missiles with impact angle constraint that met the guidance accuracy. Finally, the effectiveness of the algorithm was verified using simulation experiments.
Common Misconceptions about the Phonological Deficit Theory of Dyslexia
Authors: Share David L.
Published: November 2021

In this discussion paper, I review a number of common misconceptions about the phonological deficit theory (PDH) of dyslexia. These include the common but mistaken idea that the PDH is simply about phonemic awareness (PA), and, consequently, is a circular “pseudo”-explanation or epiphenomenon of reading difficulties. I argue that PA is only the “tip of the phonological iceberg” and that “deeper” spoken-language phonological impairments among dyslexics appear well before the onset of reading and even at birth. Furthermore, not even reading-specific expressions of phonological deficits—PA or pseudoword naming, can be considered circular if we clearly distinguish between reading proper—real meaning-bearing words, or real text, and the mechanisms (subskills) of reading development (such as phonological recoding). I also explain why an understanding of what constitutes an efficient writing system explains why phonology is necessarily a major source of variability in reading ability and hence a core deficit (or at least one core deficit) among struggling readers whether dyslexic or non-dyslexic. I also address the misguided notion that the PDH has now fallen out of favor because most dyslexia researchers have (largely) ceased studying phonological processing. I emphasize that acceptance of the PDH does not imply repudiation of other non-phonological hypotheses because the PDH does not claim to account for all the variance in reading ability/disability. Finally, I ask where neurobiology enters the picture and suggest that researchers need to exercise more caution in drawing their conclusions.