bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Week Self-Guided Internet Cognitive Behavioral Treatments for Insomnia in Adults With Situational Insomnia During the COVID-19 Outbreak
Authors: Zhang Chenxi , Yang Lulu , Liu Shuai , Xu Yan , Zheng Huirong , Zhang Bin
Published: January 2021

Objective: In the current global home confinement due to COVID-19, most individuals are facing unprecedented stress which can induce situational insomnia. We explored the efficacy of self-guided online cognitive behavioral treatment for insomnia (CBTI) on situational insomnia during the COVID-19 outbreak.

Methods: Participants were recruited from March to April in 2020 in Guangzhou, China. A 1-week Internet CBTI intervention was performed for all individuals with situational insomnia. The Pre-sleep Arousal Scale (PSAS), Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HADS) were measured before and after the intervention and compared between individuals who completed the intervention and those who did not.

Results: One hundred and ninety-four individuals with situational insomnia were included. For PSAS score, significant group effects were found on total score (p = 0.003), somatic score (p = 0.014), and cognitive score (p = 0.009). Time effect was significant on total score (p = 0.004) and cognitive score (p < 0.001). There was a significant group × time effect of the somatic score (p = 0.025). For ISI total score, there were significant time effect (p < 0.001) and group × time effect (p = 0.024). For the HADS score, a significant group effect was found on the anxiety score (p = 0.045). The HADS had significant time effects for anxiety and depressive symptoms (all p < 0.001).

Conclusion: Our study suggests good efficacy of CBTI on situational insomnia during COVID-19 for adults in the community, as well as on pre-sleep somatic hyperarousal symptom. The CBTI intervention is not applied to improve pre-sleep cognitive hyperarousal, depression, and anxiety symptoms.
Deafness Weakens Interareal Couplings in the Auditory Cortex
Authors: Yusuf Prasandhya Astagiri , Hubka Peter , Tillein Jochen , Vinck Martin , Kral Andrej
Published: January 2021

The function of the cerebral cortex essentially depends on the ability to form functional assemblies across different cortical areas serving different functions. Here we investigated how developmental hearing experience affects functional and effective interareal connectivity in the auditory cortex in an animal model with years-long and complete auditory deprivation (deafness) from birth, the congenitally deaf cat (CDC). Using intracortical multielectrode arrays, neuronal activity of adult hearing controls and CDCs was registered in the primary auditory cortex and the secondary posterior auditory field (PAF). Ongoing activity as well as responses to acoustic stimulation (in adult hearing controls) and electric stimulation applied via cochlear implants (in adult hearing controls and CDCs) were analyzed. As functional connectivity measures pairwise phase consistency and Granger causality were used. While the number of coupled sites was nearly identical between controls and CDCs, a reduced coupling strength between the primary and the higher order field was found in CDCs under auditory stimulation. Such stimulus-related decoupling was particularly pronounced in the alpha band and in top–down direction. Ongoing connectivity did not show such a decoupling. These findings suggest that developmental experience is essential for functional interareal interactions during sensory processing. The outcomes demonstrate that corticocortical couplings, particularly top-down connectivity, are compromised following congenital sensory deprivation.
The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease
Authors: Fan Dong-Yu , Sun Hao-Lun , Sun Pu-Yang , Jian Jie-Ming , Li Wei-Wei , Shen Ying-Ying , Zeng Fan , Wang Yan-Jiang , Bu Xian-Le
Published: January 2021

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.
Deep Learning-Based Classification and Voxel-Based Visualization of Frontotemporal Dementia and Alzheimer’s Disease
Authors: Hu Jingjing , Qing Zhao , Liu Renyuan , Zhang Xin , Lv Pin , Wang Maoxue , Wang Yang , He Kelei , Gao Yang , Zhang Bing
Published: January 2021

Frontotemporal dementia (FTD) and Alzheimer’s disease (AD) have overlapping symptoms, and accurate differential diagnosis is important for targeted intervention and treatment. Previous studies suggest that the deep learning (DL) techniques have the potential to solve the differential diagnosis problem of FTD, AD and normal controls (NCs), but its performance is still unclear. In addition, existing DL-assisted diagnostic studies still rely on hypothesis-based expert-level preprocessing. On the one hand, it imposes high requirements on clinicians and data themselves; On the other hand, it hinders the backtracking of classification results to the original image data, resulting in the classification results cannot be interpreted intuitively. In the current study, a large cohort of 3D T1-weighted structural magnetic resonance imaging (MRI) volumes (n = 4,099) was collected from two publicly available databases, i.e., the ADNI and the NIFD. We trained a DL-based network directly based on raw T1 images to classify FTD, AD and corresponding NCs. And we evaluated the convergence speed, differential diagnosis ability, robustness and generalizability under nine scenarios. The proposed network yielded an accuracy of 91.83% based on the most common T1-weighted sequence [magnetization-prepared rapid acquisition with gradient echo (MPRAGE)]. The knowledge learned by the DL network through multiple classification tasks can also be used to solve subproblems, and the knowledge is generalizable and not limited to a specified dataset. Furthermore, we applied a gradient visualization algorithm based on guided backpropagation to calculate the contribution graph, which tells us intuitively why the DL-based networks make each decision. The regions making valuable contributions to FTD were more widespread in the right frontal white matter regions, while the left temporal, bilateral inferior frontal and parahippocampal regions were contributors to the classification of AD. Our results demonstrated that DL-based networks have the ability to solve the enigma of differential diagnosis of diseases without any hypothesis-based preprocessing. Moreover, they may mine the potential patterns that may be different from human clinicians, which may provide new insight into the understanding of FTD and AD.
Longitudinal Association of Nut Consumption and the Risk of Cardiovascular Events: A Prospective Cohort Study in the Eastern Mediterranean Region
Authors: Mohammadifard Noushin , Ghaderian Niloufar , Hassannejad Razieh , Sajjadi Firouzeh , Sadeghi Masoumeh , Roohafza Hamidreza , Salas-Salvadó Jordi , Sarrafzadegan Nizal
Published: January 2021

Background and Aim: There are few pieces of evidence on the association between nut consumption and the risk of cardiovascular disease (CVD) in the Eastern Mediterranean Region. This study investigated the relationship of nut consumption with the risk of CVD and all-cause mortality in the Iranian population.

Methods and Results: This population-based prospective cohort study was carried out in 6,504 randomly selected participants aged ≥35 years in central Iran (2001–2013) in the framework of the Isfahan Cohort Study. Dietary data were collected by a validated 48-item food frequency questionnaire. Subjects or their next of kin were interviewed biannually, looking for the possible occurrence of cardiovascular events and all-cause mortality. During the median follow-up of 135 months and 52,704.3 person-years, we found a total of 751 CVD events. In unadjusted model, participants in the highest quartile of nut intake had a lower CVD risk {hazard ratio (HR) [95% confidence interval (CI)]: 0.57(0.47–0.70); P for trend < 0.001}, CVD mortality [HR (95% CI): 0.54 (0.33–0.72); P for trend < 0.001], and all-cause mortality [HR (95% CI): 0.24 (0.14–0.42); P for trend < 0.001]. In the fully adjusted model, the association was diluted, and no significant relationship was found between nut intake and CVD events and all-cause mortality, except for CVD mortality in the highest quartile vs. the lowest one [HR (95% CI): 0.55 (0.30–0.98)].

Conclusion: Nut intake had an inverse association with the risk of CVD mortality. It is suggested to perform studies to examine the association of individual types of nuts and different preparation methods on CVD risk and mortality.
The Inhibitory Effects of Hericium erinaceus β-glucan on in vitro Starch Digestion
Authors: Ma Bowen , Feng Tao , Zhang Sanfeng , Zhuang Haining , Chen Da , Yao Lingyun , Zhang Jingsong
Published: January 2021

β-glucan has attracted extensive attention due to its health promoting effects, such as lowering the blood sugar and lipids levels, and enhancing immunity. In this study, three different β-glucans (HEBG-1, HEBG-2, HEBG-3) were obtained from Hericium erinaceus by sodium hydroxide, β-1,3-glucanase and β-1,6-glucanase, respectively. The effects of the glucans on in vitro digestion of wheat starch were investigated by Englyst method. We found that addition of HEBGs significantly reduced the digestibility of starch, showing as decreased RDS and pGI, and increased SDS and RS content. In addition, the inhibitory effects positively correlated with the molecular weight of HEBG. The triple helix structure in HEBG plays important roles in inhibiting starch digestion. And β-1,3- glucan showed stronger inhibitor effects than those of β-1,6- glucan. This study unravels the mechanism of HEBG on inhibition of starch digestion and provides a theoretical understanding for the application of edible mushroom β-glucan to the development of low glycemic index starchy foods.
Up-regulation of L Antigen Family Member 3 Associates With Aggressive Progression of Breast Cancer
Authors: Dong Xubin , Lv Shihui , Gu Dianna , Zhang Xiaohua , Ye Zhiqiang
Published: January 2021

The role of L Antigen Family Member 3 (LAGE3) in breast cancer (BC) has not been sufficiently studied. In this study, we explored the clinical value and biological functions of LAGE3 in BC. Comprehensive analysis of LAGE3 was carried out on The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium and Gene Expression Omnibus datasets. Results showed that LAGE3 expression was higher in BC tissues than in normal breast tissues of public datasets and our local cohort. Moreover, its expression was higher in BC patients with larger tumor size, significant lymph node metastasis, higher tumor grade, and more advanced disease stage. High expression of LAGE3 was correlated with poor prognosis, and LAGE3 could independently predict survival of BC patients. Functional enrichment analysis revealed a correlation between LAGE3 expression and biochemical metabolism and immune-related terms and cancer-related pathways. Analysis of tumor microenvironment indicated that LAGE3 expression was associated with the immune cell infiltration and anti-cancer immunity cycle. LAGE3 expression was higher in triple-negative breast cancer (TNBC) compared to hormone receptor-positive BC, but not HER2-positive subtype. Suppression of LAGE3 expression inhibited the proliferation and induced apoptosis of TNBC cell lines. Besides, the down-regulation of LAGE3 attenuated the migration and invasion but reduced the expression level of epithelial-mesenchymal-transition related proteins in TNBC cell lines. In conclusion, this study demonstrated for the first time that LAGE3 promotes the progression of BC. Therefore, it may be a potential diagnostic and prognostic biomarker, as well as a treatment target for BC.
Effect of Tumor Size on Long-Term Survival After Resection for Solitary Intrahepatic Cholangiocarcinoma
Authors: Kong Junjie , Cao Yukun , Chai Jiawei , Liu Xihan , Lin Cunhu , Wang Jianping , Liu Jun
Published: January 2021

Background

The relationship between tumor size and survival in intrahepatic cholangiocarcinoma (ICC) is still controversial. This study aimed to evaluate the prognostic ability of tumor size for solitary ICC after resection and explore optimal cut-off values in different subgroups.

Methods

Patients with solitary ICC who underwent liver resection from the Surveillance, Epidemiology, and End Results Program and Shandong Provincial Hospital were retrospectively analyzed. Kaplan-Meier and Cox regression analysis were used to assess the prognostic ability of tumor size. The log-rank test was used to determine the optimal cut-off values, and a minimum P was regarded as the optimal one in different subgroups.

Results

Large tumor size groups had worse overall survival (OS) than small tumor size groups. Cox regression analysis suggested that tumor size was an independent prognostic factor for OS for solitary ICC after resection. Subgroup analysis showed tumor size was associated with OS for both solitary ICC with and without vascular invasion (VI). Furthermore, the optimal cut-off values for solitary ICC with and without VI were found to be 8 and 3 cm, respectively, which could divide the patients into two groups with significant differences in OS.

Conclusion

Tumor size was an independent prognostic factor for solitary ICC after resection. The existing American Joint Committee on Cancer (AJCC) staging system could be improved if the cut-off value of the T1 stage was changed to 8 cm and if the T2 stage incorporated a tumor size with a cut-off value of 3 cm. Further studies with more cases are needed to validate these findings.
Biological and Mechanical Synergies to Deal With Proton Therapy Pitfalls: Minibeams, FLASH, Arcs, and Gantryless Rooms
Authors: Mazal Alejandro , Vera Sanchez Juan Antonio , Sanchez-Parcerisa Daniel , Udias Jose Manuel , España Samuel , Sanchez-Tembleque Victor , Fraile Luis Mario , Bragado Paloma , Gutierrez-Uzquiza Alvaro , Gordillo Nuria , Garcia Gaston , Castro Novais Juan , Perez Moreno Juan Maria , Mayorga Ortiz Lina , Ilundain Idoate Amaia , Cremades Sendino Marta , Ares Carme , Miralbell Raymond , Schreuder Niek
Published: January 2021

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate “FLASH” irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.
DICER1 Syndrome and Cancer Predisposition: From a Rare Pediatric Tumor to Lifetime Risk
Authors: Caroleo Anna Maria , De Ioris Maria Antonietta , Boccuto Luigi , Alessi Iside , Del Baldo Giada , Cacchione Antonella , Agolini Emanuele , Rinelli Martina , Serra Annalisa , Carai Andrea , Mastronuzzi Angela
Published: January 2021

DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene. The risk to present a neoplasm before the age of 10 years is 5.3 and 31.5% before the age of 60. DICER1 variants have been associated with a syndrome involving familial pleuropulmonary blastoma (PPB), a rare malignant tumor of the lung, which occurs primarily in children under the age of 6 years and represents the most common life-threatening manifestation of DICER1 syndrome. Type I, II, III, and Ir (type I regressed) PPB are reported with a 5-year overall survival ranging from 53 to 100% (for type Ir). DICER1 gene should be screened in all patients with PPB and considered in other tumors mainly in thyroid neoplasms (multinodular goiter, thyroid cancer, adenomas), ovarian tumors (Sertoli-Leydig cell tumor, sarcoma, and gynandroblastoma), and cystic nephroma. A prompt identification of this syndrome is necessary to plan a correct follow-up and screening during lifetime.
ALT Flare Predicts Hepatocellular Carcinoma Among Antiviral Treated Patients With Chronic Hepatitis B: A Cross-Country Cohort Study
Authors: Du Yanan , Du Bingying , Fang Xiaoyan , Shu Meng , Zhang Yongjing , Chung Hsingwen , Sun Ye , Teng Jiaming , Visalath Phimphone , Qiu Hong , Cai Wei
Published: January 2021

Objectives

Alanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear.

Materials and Methods

We evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models.

Results

There were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45–4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85–11.98).

Conclusions

ALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.
YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia
Authors: Zheng Chao , Luo Jiaqian , Yang Yifan , Dong Rui , Yu Fa-Xing , Zheng Shan
Published: January 2021

Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model.

Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status.

Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model.

Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.
The Oral Microbiome in Pediatric IBD: A Source of Pathobionts or Biomarkers?
Authors: Elmaghrawy Khalid , Hussey Séamus , Moran Gary P.
Published: January 2021

The oral cavity is continuous with the gastrointestinal tract and in children, oral health may be closely linked with the overall health of the GI tract. In the case of pediatric Crohn's disease (CD), oral manifestations are an important clinical indicator of intestinal disease. Recent studies of the microbiome in IBD suggest that translocation of oral microbes to the gut may be a common feature of the microbial dysbiosis which is a signature of both CD and ulcerative colitis (UC). Murine studies suggest that translocation of oral bacteria and yeasts to the lower GI tract may trigger inflammation in susceptible hosts, providing a mechanistic link to the development of IBD. Conversely, some studies have shown that dysbiosis of the oral microbiome may occur, possibly as a result of inflammatory responses and could represent a useful source of biomarkers of GI health. This review summarizes our current knowledge of the oral microbiome in IBD and presents current hypotheses on the potential role of this community in the pathogenesis of these diseases.
Near-Infrared Spectroscopy in Extremely Preterm Infants
Authors: Pavlek Leeann R. , Mueller Clifford , Jebbia Maria R. , Kielt Matthew J. , Fathi Omid
Published: January 2021

With advances in neonatal care, survival of premature infants at the limits of viability has improved significantly. Despite these improvement in mortality, infants born at 22–24 weeks gestation are at a very high risk for short- and long-term morbidities associated with prematurity. Many of these diseases have been attributed to abnormalities of tissue oxygenation and perfusion. Near-infrared spectroscopy utilizes the unique absorption properties of oxyhemoglobin and deoxyhemoglobin to provide an assessment of regional tissue oxygen saturation, which can be used to calculate the fractional tissue oxygen extraction. This allows for a non-invasive way to monitor tissue oxygen consumption and enables targeted hemodynamic management. This mini-review provides a brief and complete overview of the background and physiology of near-infrared spectroscopy, practical use in extremely preterm infants, and potential applications in the neonatal intensive care unit. In this mini-review, we aim to summarize the three primary application sites for near-infrared spectroscopy, disease-specific indications, and available literature regarding use in extremely preterm infants.
Juglans mandshurica Maxim.: A Review of Its Traditional Usages, Phytochemical Constituents, and Pharmacological Properties
Authors: Luan Fei , Wang Ziyan , Yang Yan , Ji Yafei , Lv Haizhen , Han Keqing , Liu Daoheng , Shang Xiaofei , He Xirui , Zeng Nan
Published: January 2021

Juglans mandshurica Maxim., also known as “Manchurian walnut” (Chinese) and “Onigurumi” (Japanese), is a medicinal plant widely distributed in Western and Central Asia, especially in China. It has been traditionally used to treat cancer, gastric ulcers, diarrhea, dysentery, dermatosis, uterine prolapse, and leukopenia. To date, more than 400 constituents including quinones (e.g. naphthoquinones, anthraquinones, naphthalenones, tetralones), phenolics, flavonoids, triterpenoids, coumarins, lignans, phenylpropanoids, diarylheptanoids, and steroids, were isolated and structurally identified from different plant parts of J. mandshurica. Among them, quinones, phenolics, triterpenoids, and diarylheptanoids, as the major bioactive substances, have been extensively studied and displayed significant bioactivity. Previous studies have demonstrated that J. mandshurica and a few of its active components exhibit a wide range of pharmacologically important properties, such as antitumor, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetic, antiviral, antimicrobial, and anti-melanogenesis activities. However, many investigations on biological activities were mainly based on crude extracts of this plant, and the major bioactive ingredients responsible for these bioactivities have not been well identified. Further in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds, and more elaborate toxicity studies as well as clinical studies are needed to ensure safety and effectiveness of the plant for human use. Taken together, the present review will provide some specific useful suggestions guide to further investigations and applications of this plant in the preparation of medicines and functional foods.
Modulation of the Gut Microbiota and Liver Transcriptome by Red Yeast Rice and Monascus Pigment Fermented by Purple Monascus SHM1105 in Rats Fed with a High-Fat Diet
Authors: Yang Hua , Pan Ronghua , Wang Jing , Zheng Lizhong , Li Zhenjing , Guo Qingbin , Wang Changlu
Published: January 2021

Hyperlipidemia can easily cause atherosclerosis and induce cardiovascular and cerebrovascular diseases. Red yeast rice (RYR) contains a variety of active ingredients and is commonly used as medicine and food, and has pharmacological effects such as lowering blood lipids. In this study, we select Monascus strain SHM1105 with a high yield of Monacolin K and monascus pigment (PIG), and studied the effects of the RYR and PIG fermented by this strain on blood lipids, intestinal flora, and liver transcriptome in hyperlipidemia model rats. The experimental results show that, compared with the high-fat model group, the weight growth rate, liver weight ratio, kidney weight ratio, spleen weight ratio, and fat weight ratio of rats in the gavage lovastatin (LOV), RYR, and PIG group were all significantly decreased (p < 0.05). Intervention with RYR and PIG can significantly reduce the serum TC, TG, and LDL-C levels, which has the effect of lowering blood lipids. The 16SrDNA sequencing results showed that the ratio of Firmicutes/Bacteroidetes decreased significantly (p ≤ 0.01) after the intervention of LOV, RYR, and PIG; the abundance of the ratio of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, and Bacteroidales-S24-7-group also changed. The combined analysis of transcriptome and metabolome showed that lovastatin, RYR, and PIG can all improve lipid metabolism in rats by regulating Steroid hormone biosynthesis, Glycerolipid metabolism, and the Arachidonic acid metabolism pathway. In addition, RYR and PIG also have a unique way of regulating blood lipids. Although a lot of research on the lipid-lowering components of Monascus rice and the single pigment component of Monascus has been carried out, the actual application is RYR and pigments as mixtures, as a mixture of RYR and PIG contains a variety of biologically active ingredients, and each component may have a synergistic effect. Hence it has a lipid-lowering mechanism that lovastatin does not have. Therefore, RYR and PIG are effective in reducing lipid potential development and can be utilized in functional foods.
A Putative Serine Protease is Required to Initiate the RIPK3-MLKL—Mediated Necroptotic Death Pathway in Neutrophils
Authors: Wang Xiaoliang , Avsec Damjan , Obreza Aleš , Yousefi Shida , Mlinarič-Raščan Irena , Simon Hans-Uwe
Published: January 2021

Adhesion receptors, such as CD44, have been shown to activate receptor interacting protein kinase-3 (RIPK3)—mixed lineage kinase-like (MLKL) signaling, leading to a non-apoptotic cell death in human granulocyte/macrophage colony-stimulating factor (GM-CSF) – primed neutrophils. The signaling events of this necroptotic pathway, however, remain to be investigated. In the present study, we report the design, synthesis, and characterization of a series of novel serine protease inhibitors. Two of these inhibitors, compounds 1 and 3, were able to block CD44-triggered necroptosis in GM-CSF-primed neutrophils. Both inhibitors prevented the activation of MLKL, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3’—kinase (PI3K), hence blocking the increased levels of reactive oxygen species (ROS) required for cell death. Although compounds one and three partially inhibited isolated human neutrophil elastase (HNE) activity, we obtained no pharmacological evidence that HNE is involved in the initiation of this death pathway within a cellular context. Interestingly, neither serine protease inhibitor had any effect on FAS receptor-mediated apoptosis. Taken together, these results suggest that a serine protease is involved in non-apoptotic CD44-triggered RIPK3-MLKL-dependent neutrophil cell death, but not FAS receptor-mediated caspase-dependent apoptosis. Thus, a pharmacological block on serine proteases might be beneficial for preventing exacerbation of disease in neutrophilic inflammatory responses.
Commissioning of GPU–Accelerated Monte Carlo Code FRED for Clinical Applications in Proton Therapy
Authors: Gajewski Jan , Garbacz Magdalena , Chang Chih-Wei , Czerska Katarzyna , Durante Marco , Krah Nils , Krzempek Katarzyna , Kopeć Renata , Lin Liyong , Mojżeszek Natalia , Patera Vincenzo , Pawlik-Niedzwiecka Monika , Rinaldi Ilaria , Rydygier Marzena , Pluta Elzbieta , Scifoni Emanuele , Skrzypek Agata , Tommasino Francesco , Schiavi Angelo , Rucinski Antoni
Published: January 2021

We present commissioning and validation of Fred, a graphical processing unit (GPU)–accelerated Monte Carlo code, for two proton beam therapy facilities of different beam line design: CCB (Krakow, IBA) and EMORY (Atlanta, Varian). We followed clinical acceptance tests required to approve the certified treatment planning system for clinical use. We implemented an automated and efficient procedure to build a parameter library characterizing the clinical proton pencil beam. Beam energy, energy spread, lateral propagation model, and a dosimetric calibration factor were parametrized based on measurements performed during the facility start-up. The Fred beam model was validated against commissioning and supplementary measurements performed with and without range shifter. We obtained 1) submillimeter agreement of Bragg peak shapes in water and lateral beam profiles in air and slab phantoms, 2) <2% dose agreement for spread out Bragg peaks of different ranges, 3) average gamma index (2%/2 mm) passing rate of >95% for >1000 patient verification measurements using a two-dimensional array of ionization chambers, and 4) gamma index passing rate of >99% for three-dimensional dose distributions computed with Fred and measured with an array of ionization chambers behind an anthropomorphic phantom. The results of example treatment planning study on >100 patients demonstrated that Fred simulations in computed tomography enable an accurate prediction of dose distribution in patient and application of Fred as second patient quality assurance tool. Computation of a patient treatment in a CT using 104 protons per pencil beam took on average 2′30 min with a tracking rate of 2.9×105p+/s. Fred was successfully commissioned and validated against the clinical beam model, showing that it could potentially be used in clinical routine. Thanks to high computational performance due to GPU acceleration and an automated beam model implementation method, the application of Fred is now possible for research or quality assurance purposes in most of the proton facilities.
Estimating Parameters of Two-Level Individual-Level Models of the COVID-19 Epidemic Using Ensemble Learning Classifiers
Authors: Liu Zeyi , Deardon Rob , Fu Yanghui , Ferdous Tahsin , Ware Tony , Cheng Qing
Published: January 2021

The ongoing COVID-19 pandemic has led to a serious health crisis, and information obtained from disease transmission models fitted to observed data is needed to inform containment strategies. As the transmission of virus varies from city to city in different countries, we use a two-level individual-level model to analyze the spatiotemporal SARS-CoV-2 spread. However, inference procedures such as Bayesian Markov chain Monte Carlo, which is commonly used to estimate parameters of ILMs, are computationally expensive. In this study, we use trained ensemble learning classifiers to estimate the parameters of two-level ILMs and show that the fitted ILMs can successfully capture the virus transmission among Wuhan and 16 other cities in Hubei province, China.
Poroelasticity as a Model of Soft Tissue Structure: Hydraulic Permeability Reconstruction for Magnetic Resonance Elastography in Silico
Authors: Sowinski Damian R. , McGarry Matthew D. J. , Van Houten Elijah E. W. , Gordon-Wylie Scott , Weaver John B , Paulsen Keith D.
Published: January 2021

Magnetic Resonance Elastography allows noninvasive visualization of tissue mechanical properties by measuring the displacements resulting from applied stresses, and fitting a mechanical model. Poroelasticity naturally lends itself to describing tissue - a biphasic medium, consisting of both solid and fluid components. This article reviews the theory of poroelasticity, and shows that the spatial distribution of hydraulic permeability, the ease with which the solid matrix permits the flow of fluid under a pressure gradient, can be faithfully reconstructed without spatial priors in simulated environments. The paper describes an in-house MRE computational platform - a multi-mesh, finite element poroelastic solver coupled to an artificial epistemic agent capable of running Bayesian inference to reconstruct inhomogenous model mechanical property images from measured displacement fields. Building on prior work, the domain of convergence for inference is explored, showing that hydraulic permeabilities over several orders of magnitude can be reconstructed given very little prior knowledge of the true spatial distribution.
Weighted Low-Rank Tensor Representation for Multi-View Subspace Clustering
Authors: Wang Shuqin , Chen Yongyong , Zheng Fangying
Published: January 2021

Multi-view clustering has been deeply explored since the compatible and complementary information among views can be well captured. Recently, the low-rank tensor representation-based methods have effectively improved the clustering performance by exploring high-order correlations between multiple views. However, most of them often express the low-rank structure of the self-representative tensor by the sum of unfolded matrix nuclear norms, which may cause the loss of information in the tensor structure. In addition, the amount of effective information in all views is not consistent, and it is unreasonable to treat their contribution to clustering equally. To address the above issues, we propose a novel weighted low-rank tensor representation (WLRTR) method for multi-view subspace clustering, which encodes the low-rank structure of the representation tensor through Tucker decomposition and weights the core tensor to retain the main information of the views. Under the augmented Lagrangian method framework, an iterative algorithm is designed to solve the WLRTR method. Numerical studies on four real databases have proved that WLRTR is superior to eight state-of-the-art clustering methods.
Prevalence of Sarcopenic Obesity Using Different Definitions and the Relationship With Strength and Physical Performance in the Canadian Longitudinal Study of Aging
Authors: Purcell Sarah A. , Mackenzie Michelle , Barbosa-Silva Thiago G. , Dionne Isabelle J. , Ghosh Sunita , Siervo Mario , Ye Ming , Prado Carla M.
Published: January 2021

Sarcopenic obesity is associated with several negative health outcomes. However, the prevalence of this condition – and the relationship to physical performance parameters – varies across definitions. The aim of this cross-sectional investigation was to describe the prevalence of sarcopenic obesity using different published definitions and their relationship with handgrip strength and walking speed in older Canadian adults. Individuals aged 65+ in the Canadian Longitudinal Study on Aging (n = 11,803; 49.6% male, 50.4% female) were included. Body composition was measured using dual X-ray absorptiometry. Sarcopenic obesity was defined using 29 definitions. Low handgrip strength was identified as < 27 kg in males and < 16 kg in females and poor physical performance was defined as gait speed ≤ 0.8 m/s. The prevalence of sarcopenic obesity ranged from 0.1 to 85.3% in males, and from 0 to 80.4% in females. Sarcopenic obesity was frequently associated with low handgrip strength (p < 0.05) in both males (14/17 definitions, 82.4%) and females (21/29 definitions, 72.4%). In very few definitions, sarcopenic obesity was associated with slow gait speed (males: 1/17 definitions [6.7%]; females: 2/29 [6.9%]). In conclusion, the prevalence of sarcopenic obesity varied greatly according to definitions and sarcopenic obesity was frequently associated with low handgrip strength.
Fusion of Deep Convolution and Shallow Features to Recognize the Severity of Wheat Fusarium Head Blight
Authors: Gu Chunyan , Wang Daoyong , Zhang Huihui , Zhang Jian , Zhang Dongyan , Liang Dong
Published: January 2021

A fast and nondestructive method for recognizing the severity of wheat Fusarium head blight (FHB) can effectively reduce fungicide use and associated costs in wheat production. This study proposed a feature fusion method based on deep convolution and shallow features derived from the high-resolution digital Red-green-blue (RGB) images of wheat FHB at different disease severity levels. To test the robustness of the proposed method, the RGB images were taken under different influence factors including light condition, camera shooting angle, image resolution, and crop growth period. All images were preprocessed to eliminate background noises to improve recognition accuracy. The AlexNet model parameters trained by the ImageNet 2012 dataset were transferred to the test dataset to extract the deep convolution feature of wheat FHB. Next, the color and texture features of wheat ears were extracted as shallow features. Then, the Relief-F algorithm was used to fuse the deep convolution feature and shallow features as the final FHB features. Finally, the random forest was used to classify and identify the features of different FHB severity levels. Results show that the recognition accuracy of the proposed fusion feature model was higher than those of models using other features in all conditions. The highest recognition accuracy of severity levels was obtained when images were taken under indoor conditions, with high resolution (12 MB pixels), at 90° shooting angle during the crop filling period. The Relief-F algorithm assigned different weights to the features under different influence factors; it made the fused feature model more robust and improved the ability to recognize wheat FHB severity levels using RGB images.
The Qingdao Preschooler Facial Expression Set: Acquisition and Validation of Chinese Children’s Facial Emotion Stimuli
Authors: Chen Jie , Zhang Yulin , Zhao Guozhen
Published: January 2021

Traditional research on emotion-face processing has primarily focused on the expression of basic emotions using adult emotional face stimuli. Stimulus sets featuring child faces or emotions other than basic emotions are rare. The current study describes the acquisition and evaluation of the Qingdao Preschooler Facial Expression (QPFE) set, a facial stimulus set with images featuring 54 Chinese preschoolers’ emotion expressions. The set includes 712 standardized color photographs of six basic emotions (joy, fear, anger, sadness, surprise, and disgust), five discrete positive emotions (interest, contentment, relief, pride, and amusement), and a neutral expression. The validity of the pictures was examined based on 43 adult raters’ online evaluation, including agreement between designated emotions and raters’ labels, as well as intensity and representativeness scores. Overall, these data should contribute to the developmental and cross-cultural research on children’s emotion expressions and provide insights for future research on positive emotions.
Can Students’ Computer Programming Learning Motivation and Effectiveness Be Enhanced by Learning Python Language? A Multi-Group Analysis
Authors: Ling Hsiao-Chi , Hsiao Kuo-Lun , Hsu Wen-Chiao
Published: January 2021

Python language has become the most popular computer language. Python is widely adopted in computer courses. However, Python language’s effects on the college and university students’ learning performance, motivations, computer programming self-efficacy, and maladaptive cognition have still not been widely examined. The main objective of this study is to explore the effects of learning Python on students’ programming learning. The junior students of two classes in a college are the research participants. One class was taught Java language and the other class was taught Python language. The learning performance, motivations, and maladaptive cognition in the two classes were compared to evaluate the differences. The results showed that the motivations, computer programming self-efficacy, and maladaptive cognition on the learning performance were significant in the Python class. The results and findings of this study can be used in Python course arrangement and development.
The Merchant of Venice in Auschwitz: Taking Apart Shylock Using the SCM and BIAS Map
Authors: Knutson Susan L.
Published: January 2021

In response to Frontiers’ 2020 Call for Papers on “Stereotypes and Intercultural Relations: Interdisciplinary Integration, New Approaches, and New Contexts,” my paper integrates the scientific study of stereotypes with a literary-theatrical exploration of stereotyping. The focus is on Tibor Egervari’s post-Auschwitz adaptation of Shakespeare’s anti-Semitic comedy The Merchant of Venice, with a very brief look at his related work on Christopher Marlowe’s The Jew of Malta and his 1998 collaboration with conductor Georg Tintner on a touring production of composer Viktor Ullmann’s and librettist Peter Kien’s one-act opera, The Emperor of Atlantis, or Death’s Refusal, composed in the “model” concentration camp Terezín (Theresienstadt), in 1943–1944. Egervari’s theater art critically deconstructs what he calls “the Old Jew” stereotype in specific ways highly readable using the Stereotype Content Model (SCM) and Behavior from Intergroup Affect and Stereotypes (BIAS) map. Theater performance can sometimes embody the forceful dynamic traced by the BIAS map, from cognition to affect to behavior. Egervari’s original adapation, which sets The Merchant of Venice in Auschwitz, reveals this dynamic clearly. My interdisciplinary study of Egervari’s theatrical-cultural work validates the SCM and BIAS map for literary studies and interprets the Shylock stereotype in the terms of those models and through the lens of Egervari’s anti-Nazi adaptation of Shakespeare’s Merchant.
Systematic Parameter Reviews in Cognitive Modeling: Towards a Robust and Cumulative Characterization of Psychological Processes in the Diffusion Decision Model
Authors: Tran N.-Han , van Maanen Leendert , Heathcote Andrew , Matzke Dora
Published: January 2021

Parametric cognitive models are increasingly popular tools for analyzing data obtained from psychological experiments. One of the main goals of such models is to formalize psychological theories using parameters that represent distinct psychological processes. We argue that systematic quantitative reviews of parameter estimates can make an important contribution to robust and cumulative cognitive modeling. Parameter reviews can benefit model development and model assessment by providing valuable information about the expected parameter space, and can facilitate the more efficient design of experiments. Importantly, parameter reviews provide crucial—if not indispensable—information for the specification of informative prior distributions in Bayesian cognitive modeling. From the Bayesian perspective, prior distributions are an integral part of a model, reflecting cumulative theoretical knowledge about plausible values of the model's parameters (Lee,2018). In this paper we illustrate how systematic parameter reviews can be implemented to generate informed prior distributions for the Diffusion Decision Model (DDM; Ratcliff and McKoon,2008), the most widely used model of speeded decision making. We surveyed the published literature on empirical applications of the DDM, extracted the reported parameter estimates, and synthesized this information in the form of prior distributions. Our parameter review establishes a comprehensive reference resource for plausible DDM parameter values in various experimental paradigms that can guide future applications of the model. Based on the challenges we faced during the parameter review, we formulate a set of general and DDM-specific suggestions aiming to increase reproducibility and the information gained from the review process.
Direct Bullying and Cyberbullying: Experimental Study of Bystanders’ Motivation to Defend Victims and the Role of Anxiety and Identification With the Bully
Authors: Jungert Tomas , Karataş Pinar , Iotti Nathalie Ophelia , Perrin Sean
Published: January 2021

School bullying among young adolescents is a globally pervasive problem, but is less common when bystanders are motivated to defend victims. Thus, the focus of this experimental study is on motivation to defend victims of bullying.

Methods: A total of 388 students (Mage = 12.22 years, 49.7% girls) from two Turkish public schools (5th–8th grade) participated in a vignette experiment. Students were randomized to one of two vignettes (direct vs. cyberbullying). Self-report measures of motivation to defend, trait anxiety, depression, and identification with the victim or bully were used.

Results: Participants reported more autonomous motivation in the cyberbullying condition, while those who witnessed direct bullying reported higher anxiety and depression.

Results also revealed that this type of condition was associated with anxiety and depression, while anxiety was associated with autonomous motivation to defend. Finally, participants in the direct bullying condition were more likely to identify with the bully.

Conclusion: Findings advance our understanding of when and why adolescents are motivated to help victims of bullying because they give a richer picture of what they assess when deciding whether or not they should intervene.