bluuebunny/crossref_metadata_2025 huggingface dataset:
Entheseal Involvement in Spondyloarthritis (SpA) and Gout: An Ultrasound Comparative Study
Authors: Ventura-Ríos Lucio , Cazenave Tomas , Hernández-Díaz Cristina , Gallegos-Nava Selma , Gómez-Ruiz Citlallyc , Rosemffet Marcos , Silva-Luna Karina , Rodríguez-Henríquez Pedro , Vázquez-Mellado Janitzia , Casasola-Vargas Julio , Cruz-Arenas Esteban , de Miguel Eugenio M.
Published: May 2022

Objective

To compare the assessment of entheses in subjects with spondyloarthritis (SpA) with patients with gout by the Madrid Sonographic Enthesis Index (MASEI).

Method

This cross-sectional study includes videos of entheses evaluated by ultrasound (US) of 30 patients with SpA diagnosed according to the ASAS criteria and 30 patients with gout established by the presence of monosodium urate crystals. Entheses were evaluated for MASEI in 2 Institutes located in two different countries. Demographic and clinical data were registered. Total MASEI score, MASEI-inflammatory, and MASEI-chronic damage were analyzed. Comparisons between groups were obtained by chi-square test and Student's t-test. An inter-reading US reliability was realized.

Results

Patients with gout were older and had significantly more comorbidities than those with SpA. The total MASEI score was not significantly different among diseases (p = 0.07). MASEI-inflammatory was significantly more prevalent at the Achilles tendon in SpA, while the proximal patellar tendon was in gout. Power Doppler was higher in SpA compared to gout (p = 0.005). MASEI-chronic damage related to calcification/enthesophytes predominated in gout (p = 0.043), while calcaneal erosions did in SpA (p = 0.008). The inter-reader concordance was excellent (0.93, CI 95% 0.87–0.96, p = 0.001).

Conclusions

SpA and gout similarly involve entheses according to MASE, however, some inflammatory and chronic lesions differ significantly depending on the underlying disease and tendon scanned.
Barley Rhizosphere Microbiome Transplantation – A Strategy to Decrease Susceptibility of Barley Grown in Soils With Low Microbial Diversity to Powdery Mildew
Authors: Bziuk Nina , Maccario Lorrie , Sørensen Søren J. , Schikora Adam , Smalla Kornelia
Published: May 2022

Beneficial bacteria in the rhizosphere are known to trigger faster and stronger plant immune responses to biotic and abiotic stressors. In the present study, we aimed to test the hypothesis that a rhizosphere microbiome transplant (RMT) may improve the immune response and reduce the disease rates of barley (Hordeum vulgare). This hypothesis was tested in a greenhouse system with the powdery mildew-causing fungus Blumeria graminis f. sp. hordei (Bgh). Detached rhizosphere microbiome from barley grown in a field soil was transplanted to barley seedlings grown in potting soil with reduced microbial diversity. Saline-treated plants served as control. At the three-leaf stage, barley was infected with Bgh. Decreased susceptibility to Bgh was observed for barley treated with the RMT as displayed by lower Bgh pustule counts in a detached leaf assay. A trend toward enhanced relative transcript abundances of the defense-related genes PR1b and PR17b was observed in leaves, 24 h after the Bgh challenge, when compared to the control. Moreover, 10 days after the Bgh challenge, the barley rhizosphere microbiome was harvested and analyzed by sequencing of 16S rRNA gene amplicons. The microbial community composition was significantly influenced by the RMT and displayed higher microbial diversity compared to the control. Furthermore, microbial beta-diversity and predicted functional profiles revealed a treatment-dependent clustering. Bacterial isolates from the RMT showed in vitro plant beneficial traits related to induced resistance. Our results showed that transplantation of a rhizosphere microbiome could be a sustainable strategy to improve the health of plants grown in potting soil with low microbial diversity under greenhouse conditions.
Clinical Characteristics of Immune Response in Asymptomatic Carriers and Symptomatic Patients With COVID-19
Authors: Li Entao , Wang Shen , He Wenwen , He Jun , Liu Luogeng , Zhang Xiaotuan , Yang Songtao , Yan Feihu , Gao Yuwei , Liu Bin , Xia Xianzhu
Published: May 2022

The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major public health challenge worldwide. A comprehensive understanding of clinical characteristics and immune responses in asymptomatic carriers and symptomatic patients with COVID-19 is of great significance to the countermeasures of patients with COVID-19. Herein, we described the clinical information and laboratory findings of 43 individuals from Hunan Province, China, including 13 asymptomatic carriers and 10 symptomatic patients with COVID-19, as well as 20 healthy controls in the period from 25 January to 18 May 2020. The serum samples of these individuals were analyzed to measure the cytokine responses, receptor-binding domain (RBD), and nucleocapsid (N) protein-specific antibody titers, as well as SARS-CoV-2 neutralizing antibodies (nAbs). For cytokines, significantly higher Th1 cytokines including IL-2, IL-8, IL-12p70, IFN-γ, and TNF-α, as well as Th2 cytokines including IL-10 and IL-13 were observed in symptomatic patients compared with asymptomatic carriers. Compared with symptomatic patients, higher N-specific IgG4/IgG1 ratio and RBD-specific/N-specific IgG1 ratio were observed in asymptomatic carriers. Comparable nAbs were detected in both asymptomatic carriers and symptomatic patients with COVID-19. In the symptomatic group, nAbs in patients with underlying diseases were weaker than those of patients without underlying diseases. Our retrospective study will enrich and verify the clinical characteristics and serology diversities in asymptomatic carriers and symptomatic patients with COVID-19.
RMPFQ: A Quality-Oriented Knowledge Modelling Method for Manufacturing Systems Towards Cognitive Digital Twins
Authors: Zheng Xiaochen , Petrali Pierluigi , Lu Jinzhi , Turrin Claudio , Kiritsis Dimitris
Published: May 2022

Digital Twin is one of the fundamental enabling technologies for Industry 4.0 as it allows the convergence between a physical system and its digital representation. A proper modelling method is the prerequisite for successful digital twin implementation. The manufacturing process determines critically the quality of the manufactured products. The influential elements need to be systematically organized when modelling a manufacturing process. This paper proposes a semantic modelling method named RMPFQ (Resource, Material, Process, Function/Feature, Quality) aiming to interlink the main influential factors related to product quality during manufacturing processes. The proposed RMPFQ model is formalized with an application ontology following the IOF-Core middle-level and BFO top-level ontologies. Based on this ontology, a semantic-driven digital twin architecture is designed and mapped to the recently proposed Cognitive Digital Twin concept. A correlation matrix is designed to quantify the relationships among RMPFQ elements thus to facilitate the industrial applications. A case study based on the assembly process of a washing machine is conducted to demonstrate the implementation procedures of the proposed RMPFQ method.
Simultaneous Localization and Mapping Algorithm Based on the Asynchronous Fusion of Laser and Vision Sensors
Authors: Xing Kexin , Zhang Xingsheng , Lin Yegui , Ci Wenqi , Dong Wei
Published: May 2022

In this paper, a simultaneous localization and mapping algorithm based on the weighted asynchronous fusion of laser and vision sensors is proposed for an assistant robot. When compared to the synchronous fusion algorithm, this method can effectively use the redundant data in the vision sensor and improve the tracking accuracy of the algorithm. At the same time, the attitude estimation of the visual sensor is taken as a prior of the attitude estimation of the laser sensor to reduce the number of iterations and improve the efficiency of the algorithm. Further, according to the running state of the robot, a weighting coefficient based on angle is introduced to improve the confidence of the measurement. Experimental results show that the algorithm is robust and can work in a degraded environment. When compared to the synchronous fusion method, the asynchronous fusion algorithm has a more accurate prior, faster operation speed, higher pose estimation frequency, and more accurate positioning accuracy.
Riemannian Geometry of Functional Connectivity Matrices for Multi-Site Attention-Deficit/Hyperactivity Disorder Data Harmonization
Authors: Simeon Guillem , Piella Gemma , Camara Oscar , Pareto Deborah
Published: May 2022

The use of multi-site datasets in neuroimaging provides neuroscientists with more statistical power to perform their analyses. However, it has been shown that the imaging-site introduces variability in the data that cannot be attributed to biological sources. In this work, we show that functional connectivity matrices derived from resting-state multi-site data contain a significant imaging-site bias. To this aim, we exploited the fact that functional connectivity matrices belong to the manifold of symmetric positive-definite (SPD) matrices, making it possible to operate on them with Riemannian geometry. We hereby propose a geometry-aware harmonization approach, Rigid Log-Euclidean Translation, that accounts for this site bias. Moreover, we adapted other Riemannian-geometric methods designed for other domain adaptation tasks and compared them to our proposal. Based on our results, Rigid Log-Euclidean Translation of multi-site functional connectivity matrices seems to be among the studied methods the most suitable in a clinical setting. This represents an advance with respect to previous functional connectivity data harmonization approaches, which do not respect the geometric constraints imposed by the underlying structure of the manifold. In particular, when applying our proposed method to data from the ADHD-200 dataset, a multi-site dataset built for the study of attention-deficit/hyperactivity disorder, we obtained results that display a remarkable correlation with established pathophysiological findings and, therefore, represent a substantial improvement when compared to the non-harmonization analysis. Thus, we present evidence supporting that harmonization should be extended to other functional neuroimaging datasets and provide a simple geometric method to address it.
Not All Electrode Channels Are Needed: Knowledge Transfer From Only Stimulated Brain Regions for EEG Emotion Recognition
Authors: Perry Fordson Hayford , Xing Xiaofen , Guo Kailing , Xu Xiangmin
Published: May 2022

Emotion recognition from affective brain-computer interfaces (aBCI) has garnered a lot of attention in human-computer interactions. Electroencephalographic (EEG) signals collected and stored in one database have been mostly used due to their ability to detect brain activities in real time and their reliability. Nevertheless, large EEG individual differences occur amongst subjects making it impossible for models to share information across. New labeled data is collected and trained separately for new subjects which costs a lot of time. Also, during EEG data collection across databases, different stimulation is introduced to subjects. Audio-visual stimulation (AVS) is commonly used in studying the emotional responses of subjects. In this article, we propose a brain region aware domain adaptation (BRADA) algorithm to treat features from auditory and visual brain regions differently, which effectively tackle subject-to-subject variations and mitigate distribution mismatch across databases. BRADA is a new framework that works with the existing transfer learning method. We apply BRADA to both cross-subject and cross-database settings. The experimental results indicate that our proposed transfer learning method can improve valence-arousal emotion recognition tasks.
What Is the Relationship Between Hippocampal Neurogenesis Across Different Stages of the Lifespan?
Authors: Bond Allison M. , Ming Guo-li , Song Hongjun
Published: May 2022

Hippocampal neurogenesis has typically been studied during embryonic development or in adulthood, promoting the perception of two distinct phenomena. We propose a perspective that hippocampal neurogenesis in the mammalian brain is one continuous, lifelong developmental process. We summarize the common features of hippocampal neurogenesis that are maintained across the lifespan, as well as dynamic age-dependent properties. We highlight that while the progression of hippocampal neurogenesis across the lifespan is conserved between mammalian species, the timing of this progression is species-dependent. Finally, we discuss some current challenges in the hippocampus neurogenesis field, and future research directions to address them, such as time course analysis across the lifespan, mechanisms regulating neurogenesis progression, and interspecies comparisons. We hope that this new perspective of hippocampal neurogenesis will prompt fresh insight into previous research and inspire new directions to advance the field to identify biologically significant ways to harness the endogenous capacity for neurogenesis in the hippocampus.
Sucralose, a Non-nutritive Artificial Sweetener Exacerbates High Fat Diet-Induced Hepatic Steatosis Through Taste Receptor Type 1 Member 3
Authors: Wu Hung-Tsung , Lin Ching-Han , Pai Hsiu-Ling , Chen Yi-Cheng , Cheng Kai-Pi , Kuo Hsin-Yu , Li Chung-Hao , Ou Horng-Yih
Published: May 2022

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, and it is strongly associated with obesity. To combat obesity, artificial sweeteners are often used to replace natural sugars, and sucralose is one of the most extensively used sweeteners. It was known that sucralose exerted effects on lipid metabolism dysregulation, and hepatic inflammation; however, the effects of sucralose on hepatic steatosis were still obscure. In this study, we found that supplements of sucralose enhanced high-fat-diet (HFD)-induced hepatic steatosis. In addition, treatment of sucralose increased reactive oxygen species (ROS) generation and induced endoplasmic reticulum (ER) stress in HepG2 cells. Pretreatment of ROS or ER stress inhibitors reversed the effects of sucralose on lipogenesis. Furthermore, pretreatment of taste receptor type 1 membrane 3 (T1R3) inhibitor or T1R3 knockdown reversed sucralose-induced lipogenesis in HepG2 cells. Taken together, sucralose might activate T1R3 to generate ROS and promote ER stress and lipogenesis, and further accelerate to the development of hepatic steatosis.
Insight Into Biological Targets and Molecular Mechanisms in the Treatment of Arsenic-Related Dermatitis With Vitamin A via Integrated in silico Approach
Authors: Qin Qiuhai , Qin Lixiu , Xie Ruitang , Peng Shuihua , Guo Chao , Yang Bin
Published: May 2022

Exposure to arsenic (As), an inorganic poison, may lead to skin lesions, including dermatitis. Vitamin A (VA), a fat-soluble vitamin essential for mucous membrane integrity, plays a key role in skin protection. Although the beneficial actions of VA are known, the anti-As-related dermatitis effects of VA action remain unclear. Hence, in this study, we aimed to interpret and identify the core target genes and therapeutic mechanisms of VA action in the treatment of As-related dermatitis through integrated in silico approaches of network pharmacology and molecular docking. We integrated the key VA-biological target-signaling pathway-As-related dermatitis networks for identifying core drug targets and interaction pathways associated with VA action. The network pharmacology data indicated that VA may possess potential activity for treating As-related dermatitis through the effective regulation of core target genes. An enrichment analysis in biological processes further revealed multiple immunoregulation-associated functions, including interferon-gamma production and negative regulation of T-cell activation and production of molecular mediator of immune response. An enrichment analysis in molecular pathways mainly uncovered multiple biological signaling, including natural killer cell mediated cytotoxicity, autophagy, apoptosis, necroptosis, platelet activation involved in cell fate, and immunity regulations. Molecular docking study was used to identify docked well core target proteins with VA, including Jun, tumor protein p53 (TP53), mitogen-activated protein kinase-3 (MAPK3), MAPK1, and MAPK14. In conclusion, the potential use of VA may suppress the inflammatory stress and enhance the immunity against As-related dermatitis. In the future, VA might be useful in the treatment of dermatitis associated with As through multi-targets and multi-pathways in clinical practice.
Effects of Oat Complex High-Fiber Formula Powder on the Composition of Intestinal Microbiota and Enzyme Activities in Mice Induced by a High-Fat Diet
Authors: Huo Rui , Zhang Meili , Zhang Yakun , Bai Xue , Zhang Yuanyuan , Guo Xinyue
Published: May 2022

Using oat-corn-konjac extruded mixed powder, oat bran micro powder, skim milk powder, Pueraria whole powder, and pumpkin powder as raw materials, a formula powder with high dietary fiber was prepared, and its effect on obesity in mice with a high-fat diet was investigated. After 7 days of adaptive feeding, the mice were divided into blank group, high-fat diet group, formula powder + high-fat diet group, and weight-loss drug + high-fat diet group. After 8 weeks of treatment, the body weight of mice were observed and measured to determine the composition of tract flora, liver leptin content, insulin content, and activities of AMP-activated protein kinase (AMPK), lipoprotein lipase (LPL), fatty acid synthetase (FAS), sterol-regulatory element-binding proteins (SREBPs), and acetyl CoA carboxylase 1 (ACC1). The results indicated that treatment with the formula powder could reduce the body weight of mice and increase the abundance of Bifidobacterium, Akkermansia, and Romboutsia compared to the group given a high-fat diet. Moreover, the leptin and insulin contents of the experimental group decreased from 5.67 μg/L to 0.12 μg/L and from 12.71 μg/L to 7.13 μg/L, respectively, compared to the control group, which was not significantly different from the blank group (P > 0.05). Also, the activities of AMPK and LPL increased, and the activities of FAS, SREBPs, and ACC1 were significantly decreased (P < 0.05). Some pathogenic bacteria were significantly positively correlated with leptin and FAS and significantly negatively correlated with LPL. Some beneficial bacteria were positively correlated with LPL. Therefore, the formula powder used in this study could reduce the body weight of mice, increase the abundance of some beneficial bacteria in the colonic intestinal microbiota, and improve the activities of enzymes related to lipid metabolism in the liver. This study provides a theoretical reference for the pathway by which high-fiber diet improves liver and intestinal metabolic abnormalities.
Preparation, Characterization, and Antioxidant Properties of Phycocyanin Complexes Based on Sodium Alginate and Lysozyme
Authors: Qiao Bian-Wen , Liu Xin-Tong , Wang Chen-Xin , Song Shuang , Ai Chun-Qing , Fu Ying-Huan
Published: May 2022

In this study, phycocyanin-sodium alginate/lysozyme complex (PC-SLC) was prepared for the first time and characterized by UV spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and circular dichroism spectroscopy (CD). The stability of PC-SLC under light, temperature, pH and simulated gastrointestinal fluid was investigated. The scavenging ability of the complexes against DPPH and ABTS radicals was determined. The results showed that the complex formed by the mass ratio of SA-LZM of 0.1 showed the highest PC encapsulation rate (89.9 ± 0.374%). The combination of SA and LZM changed the secondary conformation of PC. The PC-SLC complex shows an irregular spherical structure and the spheres are clustered together. Compared with phycocyanin (PC), its thermal stability was obviously improved, but it was still greatly influenced by light. It could exist stably in simulated gastric fluid (SGF) for 2 h and be slowly digested in simulated intestinal fluid (SIF), which helped to promote the absorption of nutrients in the intestinal tract. Meanwhile, the complex PC-SLC showed high scavenging ability for DPPH and ABTS radicals. It can be concluded that the complexes have good antioxidant activity. This study provides an idea for the construction of PC delivery system and makes it more widely used in food industry and other fields.
Extent of Neck Dissection and Cervical Lymph Node Involvement in Oral Squamous Cell Carcinoma
Authors: Thoenissen Philipp , Heselich Anja , Deeg Stefanie , Al-Maawi Sarah , Tanneberger Anna , Sader Robert , Ghanaati Shahram
Published: May 2022

Introduction

Tumor resection combined with neck dissection (ND) or radiotherapy are established methods for the treatment of patients with oral squamous cell carcinoma (OSCC). However, the extent of ND can lead to postoperative complications. Therefore, for the first time, this study aims to identify lymph node involvement in OSCC performed in a bilateral systematic approach based on oncologic board meetings relying on presurgical magnetic resonance imaging (MRI) and computed tomography (CT).

Materials and Methods

In a retrospective single-center study, patients with primary OSCC resection and systematic ND performed in 4 different manners (MRND III bilateral, MRND III left and SND right, MRND III right, SND left, and SND bilateral) were examined. Lymph node involvement allocated to levels was evaluated depending on primary localization and T-stage.

Results

A total of 177 consecutive patients (mean age 63.64; 92 female, male 85) were enrolled in this study. A total of 38.98% showed cervical lymph node involvement, and metastases were found in levels 1–4. The distribution of positive lymph node metastases (n=190 LNs) was 39.47% in level 1, 38.95% in level 2, 10.53% in level 3, and 11.05% in level 4.

Discussion

In a cohort of OSCC patients with systematic bilateral ND, levels 1 and 2 had positive lymph node involvement, and no lymph node involvement was seen at level 5. Without any clinical or imaging suspicion, ND expanding 5-level MRND should be avoided regardless of the primary tumor localization, T-stage and intraoperative proof of cervical metastases.
Cell Senescence-Related Pathways Are Enriched in Breast Cancer Patients With Late Toxicity After Radiotherapy and Low Radiation-Induced Lymphocyte Apoptosis
Authors: Aguado-Flor Ester , Fuentes-Raspall María J. , Gonzalo Ricardo , Alonso Carmen , Ramón y Cajal Teresa , Fisas David , Seoane Alejandro , Sánchez-Pla Álex , Giralt Jordi , Díez Orland , Gutiérrez-Enríquez Sara
Published: May 2022

Background

Radiation-induced late effects are a common cause of morbidity among cancer survivors. The biomarker with the best evidence as a predictive test of late reactions is the radiation-induced lymphocyte apoptosis (RILA) assay. We aimed to investigate the molecular basis underlying the distinctive RILA levels by using gene expression analysis in patients with and without late effects and in whom we had also first identified differences in RILA levels.

Patients and Methods

Peripheral blood mononuclear cells of 10 patients with late severe skin complications and 10 patients without symptoms, selected from those receiving radiotherapy from 1993 to 2007, were mock-irradiated or irradiated with 8 Gy. The 48-h response was analyzed in parallel by RILA assay and gene expression profiling with Affymetrix microarrays. Irradiated and non-irradiated gene expression profiles were compared between both groups. Gene set enrichment analysis was performed to identify differentially expressed biological processes.

Results

Although differentially expressed mRNAs did not reach a significant adjusted p-value between patients suffering and not suffering clinical toxicity, the enriched pathways indicated significant differences between the two groups, either in irradiated or non-irradiated cells. In basal conditions, the main differentially expressed pathways between the toxicity and non-toxicity groups were the transport of small molecules, interferon signaling, and transcription. After 8 Gy, the differences lay in pathways highly related to cell senescence like cell cycle/NF-κB, G-protein-coupled receptors, and interferon signaling.

Conclusion

Patients at risk of developing late toxicity have a distinctive pathway signature driven by deregulation of immune and cell cycle pathways related to senescence, which in turn may underlie their low RILA phenotype.
Robot-Assisted Surgery vs Robotic Stereotactic Body Radiotherapy in Prostate Cancer: A Cost-Utility Analysis
Authors: Farah Line , Magne Nicolas , Martelli Nicolas , Sotton Sandrine , Zerbib Marc , Borget Isabelle , Scher Nathaniel , Guetta Thierry , Chargari Cyrus , Bauduceau Olivier , Toledano Alain
Published: May 2022

Prostate cancer is the most common men cancer in France. Continuous progress in oncology led to develop robot-assisted Radical Prostatectomies (rRP) and robot-assisted stereotactic body radiotherapy (rSBRT). The present study aims at comparing economic and clinical impacts of prostate cancer treatments performed either with rSBRT or rRP in France. A Markov model using TreeAge Pro software was chosen to calculate annual costs; utilities and transition probabilities of localized prostate cancer treatments. Patients were eligible for radiotherapy or surgery and the therapeutic decision was a robot-assisted intervention. Over a 10-year period, rSBRT yielded a significantly higher number of quality-adjusted life years than rRP (8.37 vs 6.85). In France, rSBRT seemed more expensive than rRP (€19,475 vs €18,968, respectively). From a societal perspective, rRP was more cost-saving (incremental cost effectiveness ratio = €332/QALY). The model was sensitive to variations of costs of the initial and recurrence state in one-way sensitivity analyses. Robot-assisted stereotactic body radiotherapy seems more cost-effective than Radical Prostatectomy in terms of QALY despite the slightly higher initial cost due to the use of radiotherapy. It would be interesting to conduct comparative quality of life studies in France over longer periods of time.
Review of Current Principles of the Diagnosis and Management of Brain Metastases
Authors: Brenner Alex W. , Patel Akash J.
Published: May 2022

Brain metastases are the most common intracranial tumors and are increasing in incidence as overall cancer survival improves. Diagnosis of brain metastases involves both clinical examination and magnetic resonance imaging. Treatment may involve a combination of surgery, radiotherapy, and systemic medical therapy depending on the patient’s neurologic status, performance status, and overall oncologic burden. Advances in these domains have substantially impacted the management of brain metastases and improved performance status and survival for some patients. Indications for surgery have expanded with improved patient selection, imaging, and intraoperative monitoring. Robust evidence supports the use of whole brain radiotherapy and stereotactic radiosurgery, for both standalone and adjuvant indications, in almost all patients. Lastly, while systemic medical therapy has historically provided little benefit, modern immunotherapeutic agents have demonstrated promise. Current investigation seeks to determine the utility of neoadjuvant radiotherapy and laser interstitial thermal therapy, which have shown benefit in limited studies to date. This article provides a review of the epidemiology, pathology, diagnosis, and treatment of brain metastases and the corresponding supporting evidence.
Necroptosis-Related LncRNAs Signature and Subtypes for Predicting Prognosis and Revealing the Immune Microenvironment in Breast Cancer
Authors: Xu Yuhao , Zheng Qinghui , Zhou Tao , Ye Buyun , Xu Qiuran , Meng Xuli
Published: May 2022

Purpose

Necroptosis is a mode of programmed cell death that overcomes apoptotic resistance. We aimed to construct a steady necroptosis-related signature and identify subtypes for prognostic and immunotherapy sensitivity prediction.

Methods

Necroptosis-related prognostic lncRNAs were selected by co-expression analysis, and were used to construct a linear stepwise regression model via univariate and multivariate Cox regression, along with least absolute shrinkage and selection operator (LASSO). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure the gene expression levels of lncRNAs included in the model. Based on the riskScore calculated, we separated patients into high- and low-risk groups. Afterwards, we performed CIBERSORT and the single-sample gene set enrichment analysis (ssGSEA) method to explore immune infiltration status. Furthermore, we investigated the relationships between the signature and immune landscape, genomic integrity, clinical characteristics, drug sensitivity, and immunotherapy efficacy.

Results

We constructed a robust necroptosis-related 22-lncRNA model, serving as an independent prognostic factor for breast cancer (BRCA). The low-risk group seemed to be the immune-activated type. Meanwhile, it showed that the higher the tumor mutation burden (TMB), the higher the riskScore. PD-L1-CTLA4 combined immunotherapy seemed to be a promising treatment strategy. Lastly, patients were assigned to 4 clusters to better discern the heterogeneity among patients.

Conclusions

The necroptosis-related lncRNA signature and molecular clusters indicated superior predictive performance in prognosis and the immune microenvironment, which may also provide guidance to drug regimens for immunotherapy and provide novel insights into precision medicine.
Glucose-6-Phosphate Dehydrogenase Deficiency and Neonatal Hyperbilirubinemia: Insights on Pathophysiology, Diagnosis, and Gene Variants in Disease Heterogeneity
Authors: Lee Heng Yang , Ithnin Azlin , Azma Raja Zahratul , Othman Ainoon , Salvador Armindo , Cheah Fook Choe
Published: May 2022

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a prevalent condition worldwide and is caused by loss-of-function mutations in the G6PD gene. Individuals with deficiency are more susceptible to oxidative stress which leads to the classical, acute hemolytic anemia (favism). However, G6PD deficiency in newborn infants presents with an increased risk of hyperbilirubinemia, that may rapidly escalate to result in bilirubin induced neurologic dysfunction (BIND). Often with no overt signs of hemolysis, G6PD deficiency in the neonatal period appears to be different in the pathophysiology from favism. This review discusses and compares the mechanistic pathways involved in these two clinical presentations of this enzyme disorder. In contrast to the membrane disruption of red blood cells and Heinz bodies formation in favism, G6PD deficiency causing jaundice is perhaps attributed to the disruption of oxidant-antioxidant balance, impaired recycling of peroxiredoxin 2, thus affecting bilirubin clearance. Screening for G6PD deficiency and close monitoring of affected infants are important aspects in neonatal care to prevent kernicterus, a permanent and devastating neurological damage. WHO recommends screening for G6PD activity of all infants in countries with high prevalence of this deficiency. The traditional fluorescent spot test as a screening tool, although low in cost, misses a significant proportion of cases with moderate deficiency or the partially deficient, heterozygote females. Some newer and emerging laboratory tests and diagnostic methods will be discussed while developments in genomics and proteomics contribute to increasing studies that spatially profile genetic mutations within the protein structure that could predict their functional and structural effects. In this review, several known variants of G6PD are highlighted based on the location of the mutation and amino acid replacement. These could provide insights on why some variants may cause a higher degree of phenotypic severity compared to others. Further studies are needed to elucidate the predisposition of some variants toward certain clinical manifestations, particularly neonatal hyperbilirubinemia, and how some variants increase in severity when co-inherited with other blood- or bilirubin-related genetic disorders.
Association of Mitochondrial DNA Polymorphisms With Pediatric-Onset Cyclic Vomiting Syndrome
Authors: Veenin Kirana , Wattanasirichaigoon Duangrurdee , Suktitipat Bhoom , Noojarern Saisuda , Lertrit Patcharee , Tim-Aroon Thipwimol , Kaewsutthi Supannee , Treepongkaruna Suporn
Published: May 2022

Background

Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder characterized by recurrent stereotypic episodes of vomiting. The pathophysiology of CVS remains obscure. Previous studies have supported the hypotheses of mitochondrial dysfunction. However, data on association studies between mitochondrial DNA (mtDNA) polymorphisms and pediatric-onset CVS are limited and inconsistent. The aims of this study were to describe clinical characteristics, evaluate association of mtDNA polymorphisms 16519T and 3010A with pediatric-onset CVS and identify new mtDNA candidate variants.

Methods

This study involved Thai patients diagnosed with CVS according to the Rome III or IV criteria before the age of 15 years. Patients' demographic data, clinical characteristics, previous investigations and treatment outcomes were obtained. Blood samples were collected for next-generation (whole exome) sequencing, followed by analysis of chromosome M (mitochondrial. Variants were filtered according to clinical significance using ClinVar and MITOMAP. mtDNA polymorphisms in 148 normal Thai individuals were used as controls.

Results

Forty-eight children were enrolled in the clinical study, and 30 participated in the genetic analysis. The median age at onset and median age at diagnosis was 3.0 (1.5–5.6) and 6.3 (3.0–8.6) years, respectively. Maternal history of migraine was positive in 16.7%. About 45.7% (21 of 46) of the patients achieved complete clinical remission, with the mean symptom duration of 5.9 ± 3.3 years. The prevalence of mtDNA variants 16519T and 3010A among the patient group and Thai general population (control) were as follows: 40.0% (12/30) vs. 27.7% (P = 0.18) and 6.7% (2/30) vs. 0.7% (P = 0.07), respectively. Five known pathogenic variants were identified in 6 patients, including mtDNA 8528C in one patient who also had infantile hypertrophic cardiomyopathy. Six likely pathogenic variants were found but without statistical significance. We identified 11 variants with significant prevalence in the patient group. Though, these variants were classified as variants of unknown significance (VUS), several of them were located in mt functional regions and therefore they deserve further investigations as new candidates for association with pediatric CVS.

Conclusion

There were no associations of mtDNA polymorphisms 16519T and 3010A with CVS in our pediatric cohort. Five pathogenic variants and 11 VUS were found associated with pediatric-onset CVS.
Rhoifolin Alleviates Alcoholic Liver Disease In Vivo and In Vitro via Inhibition of the TLR4/NF-κB Signaling Pathway
Authors: Mai Baoyu , Han Ling , Zhong Jiarui , Shu Jingqi , Cao Zelin , Fang Jiaqi , Zhang Xiaoying , Gao Zelin , Xiao Fengxia
Published: May 2022

Background: Alcoholic liver disease (ALD) is a common chronic liver disorder worldwide, which is detrimental to human health. A preliminary study showed that the total flavonoids within Citrus grandis “Tomentosa” exerted a remarkable effect on the treatment of experimental ALD. However, the active substances of Citrus grandis “Tomentosa” were not elucidated. Rhoifolin (ROF) is a flavonoid component present in high levels. Therefore, this research aimed to evaluate the hepatoprotective effects of ROF and its possible mechanisms.

Methods: Molecular docking was performed to analyze the binding energy of ROF to the main target proteins related to ALD. Subsequently, mice were fed ethanol (ETH) for 49 days to establish the chronic alcoholic liver injury models. The liver pathological injury, serum aminotransferase levels, and oxidative stress levels in the liver tissue were measured. Human normal hepatocytes (LO2 cells) were incubated with ETH to construct the alcoholic liver cell model. The inflammatory markers and apoptosis factors were evaluated using real-time PCR and flow cytometry. Finally, the effects of ROF on the CYP2E1 and NF-κB signaling pathways were tested in vitro and in vivo.

Results: Molecular docking results demonstrated that ROF was able to successfully dock with the target proteins associated with ALD. In animal studies, ROF attenuated ETH-induced liver damage in mice by decreasing the serum concentrations of AST and ALT, reducing the expression of inflammatory cytokines, and maintaining antioxidant balance in the liver tissue. The in vitro experiments demonstrated that ROF suppressed ETH-induced apoptosis in LO2 cells by promoting Bcl-2 mRNA and inhibiting Bax mRNA and caspase 3 protein expression. ROF decreased the level of LDH, ALT, AST, ROS, and MDA in the supernatant; induced the activity of GSH and SOD; and inhibited TNF-α, IL-6, and IL-1β expression levels. Mechanistically, ROF could significantly downregulate the expression levels of CYP2E1, TLR4, and NF-κB phosphorylation.

Conclusion: This study indicates that ROF is the active component within the total flavonoids, which may alleviate ETH-induced liver injury by inhibiting NF-κB phosphorylation. Therefore, ROF may serve as a promising compound for treating ALD.
Does Plasma Inhibit the Activity of KCl Cotransport in Red Cells From LK Sheep?
Authors: Lu David C.-Y. , Hannemann Anke , Gibson John S.
Published: May 2022

Red cells from LK sheep represent an important paradigm for control of KCl cotransport activity, as well as being important to sheep erythroid function. A previous report (Godart et al., 1997) suggested that autologous plasma markedly inhibits red cell KCC activity and identified the presence of the bicarbonate/CO2 buffer system as the probable cause. Findings were restricted, however, to red cells from patients with sickle cell disease (SCD) swollen anisotonically and carried out at a very high O2 tension (c.700 mmHg). It was therefore important to investigate the generality of the effect described and whether it was also relevant to the two main stimuli for KCC activity encountered most often by circulating red cells in vivo - low pH in active muscle beds during exercise and high urea concentrations in the renal medulla during antidiuresis. Results confirm that inhibition was significant in response to anisotonic swelling with KCC activity in MOPS-buffered saline (MBS) vs. bicarbonate-buffered saline (BBS) and in MBS vs. plasma both reduced (by about 25 and 50%, respectively). By contrast, however, inhibition was absent at low pH and in high concentrations of urea. These findings suggest therefore that red cell KCC activity represents an important membrane permeability in vivo in red cells suspended in plasma. They are relevant, in particular, to sheep red cells, and may also be important by extension to those of other species and to the abnormal red cells found in human patients with SCD.
CASM-AMFMNet: A Network Based on Coordinate Attention Shuffle Mechanism and Asymmetric Multi-Scale Fusion Module for Classification of Grape Leaf Diseases
Authors: Suo Jiayu , Zhan Jialei , Zhou Guoxiong , Chen Aibin , Hu Yaowen , Huang Weiqi , Cai Weiwei , Hu Yahui , Li Liujun
Published: May 2022

Grape disease is a significant contributory factor to the decline in grape yield, typically affecting the leaves first. Efficient identification of grape leaf diseases remains a critical unmet need. To mitigate background interference in grape leaf feature extraction and improve the ability to extract small disease spots, by combining the characteristic features of grape leaf diseases, we developed a novel method for disease recognition and classification in this study. First, Gaussian filters Sobel smooth de-noising Laplace operator (GSSL) was employed to reduce image noise and enhance the texture of grape leaves. A novel network designated coordinated attention shuffle mechanism-asymmetric multi-scale fusion module net (CASM-AMFMNet) was subsequently applied for grape leaf disease identification. CoAtNet was employed as the network backbone to improve model learning and generalization capabilities, which alleviated the problem of gradient explosion to a certain extent. The CASM-AMFMNet was further utilized to capture and target grape leaf disease areas, therefore reducing background interference. Finally, Asymmetric multi-scale fusion module (AMFM) was employed to extract multi-scale features from small disease spots on grape leaves for accurate identification of small target diseases. The experimental results based on our self-made grape leaf image dataset showed that, compared to existing methods, CASM-AMFMNet achieved an accuracy of 95.95%, F1 score of 95.78%, and mAP of 90.27%. Overall, the model and methods proposed in this report could successfully identify different diseases of grape leaves and provide a feasible scheme for deep learning to correctly recognize grape diseases during agricultural production that may be used as a reference for other crops diseases.
WSRD-Net: A Convolutional Neural Network-Based Arbitrary-Oriented Wheat Stripe Rust Detection Method
Authors: Liu Haiyun , Jiao Lin , Wang Rujing , Xie Chengjun , Du Jianming , Chen Hongbo , Li Rui
Published: May 2022

Wheat stripe rusts are responsible for the major reduction in production and economic losses in the wheat industry. Thus, accurate detection of wheat stripe rust is critical to improving wheat quality and the agricultural economy. At present, the results of existing wheat stripe rust detection methods based on convolutional neural network (CNN) are not satisfactory due to the arbitrary orientation of wheat stripe rust, with a large aspect ratio. To address these problems, a WSRD-Net method based on CNN for detecting wheat stripe rust is developed in this study. The model is a refined single-stage rotation detector based on the RetinaNet, by adding the feature refinement module (FRM) into the rotation RetinaNet network to solve the problem of feature misalignment of wheat stripe rust with a large aspect ratio. Furthermore, we have built an oriented annotation dataset of in-field wheat stripe rust images, called the wheat stripe rust dataset 2021 (WSRD2021). The performance of WSRD-Net is compared to that of the state-of-the-art oriented object detection models, and results show that WSRD-Net can obtain 60.8% AP and 73.8% Recall on the wheat stripe rust dataset, higher than the other four oriented object detection models. Furthermore, through the comparison with horizontal object detection models, it is found that WSRD-Net outperforms horizontal object detection models on localization for corresponding disease areas.
Direct Human-AI Comparison in the Animal-AI Environment
Authors: Voudouris Konstantinos , Crosby Matthew , Beyret Benjamin , Hernández-Orallo José , Shanahan Murray , Halina Marta , Cheke Lucy G.
Published: May 2022

Artificial Intelligence is making rapid and remarkable progress in the development of more sophisticated and powerful systems. However, the acknowledgement of several problems with modern machine learning approaches has prompted a shift in AI benchmarking away from task-oriented testing (such as Chess and Go) towardsability-oriented testing, in which AI systems are tested on their capacity to solve certainkindsof novel problems. The Animal-AI Environment is one such benchmark which aims to apply the ability-oriented testing used in comparative psychology to AI systems. Here, we present the first direct human-AI comparison in the Animal-AI Environment, using children aged 6–10 (n = 52). We found that children of all ages were significantly better than a sample of 30 AIs across most of the tests we examined, as well as performing significantly better than the two top-scoring AIs, “ironbar” and “Trrrrr,” from the Animal-AI Olympics Competition 2019. While children and AIs performed similarly on basic navigational tasks, AIs performed significantly worse in more complex cognitive tests, including detour tasks, spatial elimination tasks, and object permanence tasks, indicating that AIs lack several cognitive abilities that children aged 6–10 possess. Both children and AIs performed poorly on tool-use tasks, suggesting that these tests are challenging for both biological and non-biological machines.
The Functions of the Board of Directors in Corporate Philanthropy: An Empirical Study From China
Authors: Pan Qi , Huang Zhangjie
Published: May 2022

As an important way for enterprises to fulfill social responsibility, corporate philanthropy (CP) has attracted much attention from the academic community. But there are still few well-targeted theoretical and empirical studies on what functions the board of directors (BOD) should perform to better fulfill philanthropic responsibilities. Taking this deficiency as a breakthrough, this study focuses on Chinese state-owned and private enterprises to analyze and test the functions performed by the BOD in CP. Based on the sample of Chinese A-share listed companies from 2008 to 2019, the empirical results show that the BOD of state-owned enterprises mainly performs a monitoring function in CP while that of private enterprises mainly performs a consulting function. The above findings remain valid when potential biases in the quantitative analysis are considered. Further research shows that environmental dynamism and board fault lines inhibit the performance of the above two functions. The contributions of the study include clarifying the functional characteristics of the BOD in CP and its influencing factors, revealing new theories to the formation mechanism of CP, which provide references for enterprises to optimize philanthropic decision-making. The limitation should also be emphasized that our findings are based only on Chinese contexts.
A Unified Model of Resilience and Aging: Applications to COVID-19
Authors: Wister Andrew , Klasa Katarzyna , Linkov Igor
Published: May 2022

Drawing on multidisciplinary research focusing on a spectrum ranging from individual experience to structural system-level risk response and resilience, this article develops a rationale for a Unified Model of Resilience and Aging (UMRA). In response to a broad range of adversities associated with aging, it details the ways in which some individuals are able to bounce back better than others, or adapt better than expected, termed resilience. However, resilience and aging theoretical models have developed out of different disciplinary developments, ranging from individual levels to structural level complex systems, including several gerontological theoretical models addressing adaptation to life course and aging processes. The article reviews and synthesizes prior conceptual and theoretical work, and their empirical groundings, in order to develop an integrated resilience model with wide applications to aging-related problems including chronic illness, mental health, widowhood, poverty, caregiving burden, etc. The article focuses specifically on COVID-19 pandemic risk, response and resilience in order to specify applications of the UMRA, and to suggest avenues for future research and testing of theoretical axioms.
Independent Agencies and Research Program Performance
Authors: Keckler Charles N. W.
Published: May 2022

Combining performance data from the Bush Administration's Program Assessment Rating Tool (PART) initiative with measures of organizational independence, I examine whether insulated and plural leadership structures are consequential for the outcomes of the federal programs administered by them. Using regression modeling and controlling for program type, I find that embedding programs in independent agencies is positively and significantly related to ratings of program performance. The effects of independent commissions appear mediated in these models by their positive association with the PART scores given to certain program types, notably research programs. These results are problematic for any global attribution of greater effectiveness to executive agencies under single-headed control and closer presidential direction.