bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations of the Gut Microbiome and Metabolome in Patients With Proliferative Diabetic Retinopathy
Authors: Ye Panpan , Zhang Xueyou , Xu Yufeng , Xu Jia , Song Xiaoxiao , Yao Ke
Published: September 2021

Diabetic retinopathy (DR) has been reported to associate with gut microbiota alterations in murine models and thus “gut-retina-axis” has been proposed. However, the role of gut microbiome and the associated metabolism in DR patients still need to be elucidated. In this study, we collected fecal samples from 45 patients with proliferative diabetic retinopathy (PDR) and 90 matched diabetic patients (1:2 according to age, sex, and duration of diabetes) without DR (NDR) and performed 16S rRNA gene sequencing and untargeted metabolomics. We observed significantly lower bacterial diversity in the PDR group than that in the NDR group. Differential gut bacterial composition was also found, with significant depletion of 22 families (e.g., Coriobacteriaceae, Veillonellaceae, and Streptococcaceae) and enrichment of two families (Burkholderiaceae and Burkholderiales_unclassified) in the PDR group as compared with the NDR group. There were significantly different fecal metabolic features, which were enriched in metabolic pathways such as arachidonic acid and microbial metabolism, between the two groups. Among 36 coabundance metabolite clusters, 11 were positively/negatively contributed to PDR using logistic regression analysis. Fifteen gut microbial families were significantly correlated with the 11 metabolite clusters. Furthermore, a fecal metabolite-based classifier was constructed to distinguish PDR patients from NDR patients accurately. In conclusion, PDR is associated with reduced diversity and altered composition of gut microbiota and specific microbe-metabolite interplay. Our findings help to better understand the disease pathogenesis and provide novel diagnostic and therapeutic targets for PDR.
Targeting the Achilles Heel of FtsZ: The Interdomain Cleft
Authors: Pradhan Pinkilata , Margolin William , Beuria Tushar Kant
Published: September 2021

Widespread antimicrobial resistance among bacterial pathogens is a serious threat to public health. Thus, identification of new targets and development of new antibacterial agents are urgently needed. Although cell division is a major driver of bacterial colonization and pathogenesis, its targeting with antibacterial compounds is still in its infancy. FtsZ, a bacterial cytoskeletal homolog of eukaryotic tubulin, plays a highly conserved and foundational role in cell division and has been the primary focus of research on small molecule cell division inhibitors. FtsZ contains two drug-binding pockets: the GTP binding site situated at the interface between polymeric subunits, and the inter-domain cleft (IDC), located between the N-terminal and C-terminal segments of the core globular domain of FtsZ. The majority of anti-FtsZ molecules bind to the IDC. Compounds that bind instead to the GTP binding site are much less useful as potential antimicrobial therapeutics because they are often cytotoxic to mammalian cells, due to the high sequence similarity between the GTP binding sites of FtsZ and tubulin. Fortunately, the IDC has much less sequence and structural similarity with tubulin, making it a better potential target for drugs that are less toxic to humans. Over the last decade, a large number of natural and synthetic IDC inhibitors have been identified. Here we outline the molecular structure of IDC in detail and discuss how it has become a crucial target for broad spectrum and species-specific antibacterial agents. We also outline the drugs that bind to the IDC and their modes of action.
Correlation of Decreased Serum Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Levels With Non-motor Symptoms in Patients With Parkinson’s Disease
Authors: Hu Shiyu , Huang Shen , Ma Jianjun , Li Dongsheng , Zhao Zhenxiang , Zheng Jinhua , Li Mingjian , Wang Zhidong , Sun Wenhua , Shi Xiaoxue
Published: September 2021

Objective: Pituitary adenylate-cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuropeptides that exhibit anti-inflammatory and neuroprotective properties, modulating the production of cytokines and chemokines, and the behavior of immune cells. However, the relationship between PACAP and VIP levels and Parkinson’s disease (PD) are not clear. The aim of the current study was to evaluate serum PACAP and VIP levels in PD patients and to analysis the correlation between neuropeptide levels and non-motor symptoms.

Methods: In this cross-sectional study, we enrolled 72 patients with idiopathic PD and 71 healthy volunteers. Serum PACAP and VIP levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS) for PD, including total and single-item scores.

Results: The serum PACAP levels of PD patients were significantly lower than those of healthy controls [(76.02 ± 43.78) pg/ml vs. (154.96 ± 76.54) pg/ml, P < 0.001]; and the serum VIP levels of PD patients were also significantly lower than those of healthy controls [(109.56 ± 15.39) pg/ml vs. (136.46 ± 24.16) pg/ml, P < 0.001]. PACAP levels were inversely correlated only with the score on NMSS item five, assessing Attention/memory (r = −0.276, P < 0.05) and lower serum PACAP levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [(61.87 ± 32.66) pg/ml vs. (84.51 ± 47.59) pg/ml, P < 0.05]; meanwhile, VIP levels were inversely correlated with the NMSS total score (r = −0.285, P < 0.05) and the single-item scores for item one, assessing Cardiovascular (r = −0.257, P < 0.05) and item three, assessing Mood/cognition (r = −0.373, P < 0.05), and lower serum VIP levels were detected in the anxiety subgroup and depression subgroup than in the non-anxiety subgroup and non-depression subgroup, respectively [(107.45 ± 15.40) pg/ml vs. (116.41 ± 13.67) pg/ml, P < 0.05]; [(104.45 ± 15.26) pg/ml vs. (113.43 ± 14.52) pg/ml, P < 0.05].

Conclusion: The serum PACAP and VIP levels of PD patients were significantly lower than those of healthy controls. The non-motor symptoms significantly negatively correlated with serum PACAP level was cognitive dysfunction, while mood disorder was significantly correlated with serum VIP level.
Total Cerebral Small Vessel Disease Burden on MRI Correlates With Medial Temporal Lobe Atrophy and Cognitive Performance in Patients of a Memory Clinic
Authors: Fan Yangyi , Shen Ming , Huo Yang , Gao Xuguang , Li Chun , Zheng Ruimao , Zhang Jun
Published: September 2021

Background: Cerebral small vessel disease (cSVD) and neurodegeneration are the two main causes of dementia and are considered distinct pathological processes, while studies have shown overlaps and interactions between the two pathological pathways. Medial temporal atrophy (MTA) is considered a classic marker of neurodegeneration. We aimed to investigate the relationship of total cSVD burden and MTA on MRI using a total cSVD score and to explore the impact of the two MRI features on cognition.

Methods: Patients in a memory clinic were enrolled, who underwent brain MRI scan and cognitive evaluation within 7 days after the first visit. MTA and total cSVD score were rated using validated visual scales. Cognitive function was assessed by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales. Spearman's correlation and regression models were used to test (i) the association between MTA and total cSVD score as well as each cSVD marker and (ii) the correlation of the MRI features and cognitive status.

Results: A total of 312 patients were finally enrolled, with a median age of 75.0 (66.0–80.0) years and 40.7% (127/312) males. All of them finished MRI and MMSE, and 293 subjects finished MoCA. Of note, 71.8% (224/312) of the patients had at least one of the cSVD markers, and 48.7% (152/312) of them had moderate–severe MTA. The total cSVD score was independently associated with MTA levels, after adjusting for age, gender, years of education, and other vascular risk factors (OR 1.191, 95% CI 1.071–1.324, P = 0.001). In regard to individual markers, a significant association existed only between white matter hyperintensities and MTA after adjusting for the factors mentioned above (OR 1.338, 95% CI 1.050–1.704, P = 0.018). Both MTA and total cSVD score were independent risk factors for MMSE ≤ 26 (MTA: OR 1.877, 95% CI 1.407–2.503, P < 0.001; total cSVD score: OR 1.474, 95% CI 1.132–1.921, P = 0.004), and MoCA < 26 (MTA: OR 1.629, 95% CI 1.112–2.388, P = 0.012; total cSVD score: OR 1.520, 95% CI 1.068–2.162, P = 0.020). Among all the cSVD markers, microbleed was found significantly associated with MMSE ≤ 26, while no marker was demonstrated a relationship with MoCA < 26.

Conclusion: Cerebral small vessel disease was related to MTA in patients of a memory clinic, and both the MRI features had a significant association with cognitive impairment.
Identification of Emotion Using Electroencephalogram by Tunable Q-Factor Wavelet Transform and Binary Gray Wolf Optimization
Authors: Li Siyu , Lyu Xiaotong , Zhao Lei , Chen Zhuangfei , Gong Anmin , Fu Yunfa
Published: September 2021

Emotional brain-computer interface based on electroencephalogram (EEG) is a hot issue in the field of human-computer interaction, and is also an important part of the field of emotional computing. Among them, the recognition of EEG induced by emotion is a key problem. Firstly, the preprocessed EEG is decomposed by tunable-Q wavelet transform. Secondly, the sample entropy, second-order differential mean, normalized second-order differential mean, and Hjorth parameter (mobility and complexity) of each sub-band are extracted. Then, the binary gray wolf optimization algorithm is used to optimize the feature matrix. Finally, support vector machine is used to train the classifier. The five types of emotion signal samples of 32 subjects in the database for emotion analysis using physiological signal dataset is identified by the proposed algorithm. After 6-fold cross-validation, the maximum recognition accuracy is 90.48%, the sensitivity is 70.25%, the specificity is 82.01%, and the Kappa coefficient is 0.603. The results show that the proposed method has good performance indicators in the recognition of multiple types of EEG emotion signals, and has a better performance improvement compared with the traditional methods.
Posterior Interosseous Fascicular Constriction Within the Radial Nerve in a Diabetic Patient With Bilateral Neuralgic Amyotrophy: A Case Report
Authors: Kim Woojun , Kang Soo Hwan , An Jae Young
Published: September 2021

Background: Neuralgic amyotrophy (NA) is an acute, monophasic, painful inflammatory dysimmune focal, or multifocal mononeuropathy. The lesion in NA is not always restricted to the brachial plexus but also involves individual nerves or branches. The prognosis of NA is less favorable than previously assumed, but the reasons for poor recovery remain unknown. Nerve constriction may be one of the causes of poor prognosis in NA.

Case Presentation: Herein, we described a 54-year-old male with a history of type 2 diabetes in whom bilateral neuralgic amyotrophy developed with constriction of the posterior interosseous fascicle within the radial nerve. The patient experienced sudden-onset severe pain in both shoulders followed, 2 days later, by weakness in bilateral shoulders and the left forearm extensors over the subsequent month. The left forearm extensors were more severely affected than both shoulder girdle muscles. He noted a 7-kg weight loss for 1 month before pain onset. After diagnosing diabetic NA based on the clinical symptoms, imaging, and electrophysiological studies, treatment with systemic steroids improved pain and weakness in both shoulder muscles. Weakness in the left forearm extensors persisted after 1 month of steroid treatment. Follow-up ultrasound revealed constriction of the posterior interosseous fascicle within the main trunk of the left radial nerve at the elbow. Surgical exploration at 6 months after onset identified fascicle constriction, for which neurolysis was performed. Weakness in the extensors of the wrist and fingers did not improve during the 16-month follow-up.

Conclusion: A single constriction of the fascicle within a peripheral nerve may often be under-recognized if NA presents with variable degrees of weakness in bilateral upper limbs. Furthermore, fascicular constriction without edema of the parent nerve may be easily missed on the initial ultrasound. A lack of early recognition of nerve constriction and delay in surgical intervention can result in unfavorable outcomes. The physician should consider the possibility of the fascicular constriction when evaluating patients suspected of brachial NA with significant weakness in the distal upper limb compared to the proximal weakness or weakness of the distal upper limb that does not improve over time.
Age-Related Disparities in Stroke Knowledge Among Community Older Adults
Authors: Liu Xiaochuan , Gui Huiwen , Yao Sichen , Li Zhongcheng , Zhao Jing
Published: September 2021

Background: This study aimed to investigate the disparities in stroke knowledge between older adults and the oldest old.

Methods: Family physicians conducted a cross-sectional survey through face-to-face interviews with the older and oldest old adults of two suburban communities in the Minhang district, Shanghai between October 1, 2020, and November 30, 2020. All participants were classified as oldest old (age ≥80 years) and older adults (age 60–79 years). Between-group differences in stroke knowledge were investigated by multivariate logistic regression analysis.

Results: Overall, 466 older adults including 101 (21.67%) oldest old persons were qualified. Older adults were more familiar with the risk factors and symptoms of stroke than the oldest old. By multivariable logistic regression analysis, older adults were more familiar with the following risk factors: smoking [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.16–0.61], alcohol abuse (OR 0.45, 95% CI 0.23–0.87), dyslipidemia (OR 0.51, 95% CI 0.31–0.85), and obesity (OR 0.30, 95% CI 0.17–0.53) than the oldest old. Regarding stroke symptoms, older adults were more aware regarding vision alteration (OR 0.42, 95% CI 0.25–0.69) and face-drop (OR 0.57, 95% CI 0.35–0.95) than the oldest old. The oldest old were less aware of acute stroke therapy (OR 0.11, 95% CI 0.02–0.48) and calling the emergency medical service (OR 0.30, 95% CI 0.12–0.70) than older adults. Finally, the older adults used television (OR 0.53, 95% CI 0.28–1.0), WeChat (OR 0.21, 95% CI 0.05–0.89), and the community bulletin board (OR 0.43, 95% CI 0.23–0.80) as knowledge sources more than the oldest old.

Conclusion: The older adults and the oldest old had significantly high disparities in stroke knowledge. Given the aging population across China, the life expectancy is expected to be longer in future decades. These differences should be addressed in stroke educational campaigns targeting the oldest old.
Maternal Prenatal Stress, Thyroid Function and Neurodevelopment of the Offspring: A Mini Review of the Literature
Authors: Anifantaki Foteini , Pervanidou Panagiota , Lambrinoudaki Irene , Panoulis Konstantinos , Vlahos Nikos , Eleftheriades Makarios
Published: September 2021

Fetal brain is extremely plastic and vulnerable to environmental influences that may have long-term impact on health and development of the offspring. Both the Hypothalamic-Pituitary-Adrenal (HPA) and the Hypothalamic-Pituitary-Thyroid (HPT) axes are involved in stress responses, whereas, their final effectors, the Glucocorticoids (GCs) and the Thyroid Hormones (TH s), mediate several fundamental processes involved in neurodevelopment. The effects of these hormones on brain development are found to be time and dose-dependent. Regarding THs, the developing fetus depends on maternal supply of hormones, especially in the first half of pregnancy. It is acknowledged that inadequate or excess concentrations of both GCs and THs can separately cause abnormalities in the neuronal and glial structures and functions, with subsequent detrimental effects on postnatal neurocognitive function. Studies are focused on the direct impact of maternal stress and GC excess on growth and neurodevelopment of the offspring. Of particular interest, as results from recent literature data, is building understanding on how chronic stress and alterations of the HPA axis interacts and influences HPT axis and TH production. Animal studies have shown that increased GC concentrations related to maternal stress, most likely reduce maternal and thus fetal circulating THs, either directly or through modifications in the expression of placental enzymes responsible for regulating hormone levels in fetal microenvironment. The purpose of this review is to provide an update on data regarding maternal stress and its impact on fetal neurodevelopment, giving particular emphasis in the interaction of two axes and the subsequent thyroid dysfunction resulting from such circumstances.
Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis
Authors: Ebstein Frédéric , Küry Sébastien , Papendorf Jonas Johannes , Krüger Elke
Published: September 2021

Over thirty years have passed since the first description of ubiquitin-positive structures in the brain of patients suffering from Alzheimer’s disease. Meanwhile, the intracellular accumulation of ubiquitin-modified insoluble protein aggregates has become an indisputable hallmark of neurodegeneration. However, the role of ubiquitin and a fortiori the ubiquitin-proteasome system (UPS) in the pathogenesis of neurodevelopmental disorders (NDD) is much less described. In this article, we review all reported monogenic forms of NDD caused by lesions in genes coding for any component of the UPS including ubiquitin-activating (E1), -conjugating (E2) enzymes, ubiquitin ligases (E3), ubiquitin hydrolases, and ubiquitin-like modifiers as well as proteasome subunits. Strikingly, our analysis revealed that a vast majority of these proteins have a described function in the negative regulation of the innate immune response. In this work, we hypothesize a possible involvement of autoinflammation in NDD pathogenesis. Herein, we discuss the parallels between immune dysregulation and neurodevelopment with the aim at improving our understanding the biology of NDD and providing knowledge required for the design of novel therapeutic strategies.
Assessing the Role of Carotenoid Cleavage Dioxygenase 4 Homoeologs in Carotenoid Accumulation and Plant Growth in Tetraploid Wheat
Authors: Yu Shu , Tian Li
Published: September 2021

The dietary needs of humans for provitamin A carotenoids arise from their inability to synthesize vitamin A de novo. To improve the status of this essential micronutrient, special attention has been given to biofortification of staple foods, such as wheat grains, which are consumed in large quantities but contain low levels of provitamin A carotenoids. However, there remains an unclear contribution of metabolic genes and homoeologs to the turnover of carotenoids in wheat grains. To better understand carotenoid catabolism in tetraploid wheat, Targeting Induced Local Lesions in Genomes (TILLING) mutants of CCD4, encoding a Carotenoid Cleavage Dioxygenase (CCD) that cleaves carotenoids into smaller apocarotenoid molecules, were isolated and characterized. Our analysis showed that ccd4 mutations co-segregated with Poltergeist-like (pll) mutations in the TILLING mutants of A and B subgenomes, hence the ccd-A4 pll-A, ccd-B4 pll-B, and ccd-A4 ccd-B4 pll-A pll-B mutants were analyzed in this study. Carotenoid profiles are comparable in mature grains of the mutant and control plants, indicating that CCD4 homoeologs do not have a major impact on carotenoid accumulation in grains. However, the neoxanthin content was increased in leaves of ccd-A4 ccd-B4 pll-A pll-B relative to the control. In addition, four unidentified carotenoids showed a unique presence in leaves of ccd-A4 ccd-B4 pll-A pll-B plants. These results suggested that CCD4 homoeologs may contribute to the turnover of neoxanthin and the unidentified carotenoids in leaves. Interestingly, abnormal spike, grain, and seminal root phenotypes were also observed for ccd-A4 pll-A, ccd-B4 pll-B, and ccd-A4 ccd-B4 pll-A pll-B plants, suggesting that CCD4 and/or PLL homoeologs could function toward these traits. Overall, this study not only reveals the role of CCD4 in cleavage of carotenoids in leaves and grains, but also uncovers several critical growth traits that are controlled by CCD4, PLL, or the CCD4-PLL interaction.
Decreased IL-6 and NK Cells in Early-Stage Lung Adenocarcinoma Presenting as Ground-Glass Opacity
Authors: Zhang Pengfei , He Boxue , Cai Qidong , Tu Guangxu , Peng Xiong , Zhao Zhenyu , Peng Weilin , Yu Fenglei , Wang Min , Tao Yongguang , Wang Xiang
Published: September 2021

Background

Lung ground-glass opacities (GGOs) are an early manifestation of lung adenocarcinoma. It is of great value to study the changes in the immune microenvironment of GGO to elucidate the occurrence and evolution of early lung adenocarcinoma. Although the changes of IL-6 and NK cells in lung adenocarcinoma have caught global attention, we have little appreciation for how IL-6 and NK cells in the lung GGO affect the progression of early lung adenocarcinoma.

Methods

We analyzed the RNA sequencing data of surgical specimens from 21 patients with GGO-featured primary lung adenocarcinoma and verified the changes in the expression of IL-6 and other important immune molecules in the TCGA and GEO databases. Next, we used flow cytometry to detect the protein expression levels of important Th1/Th2 cytokines in GGO and normal lung tissues and the changes in the composition ratio of tumor infiltrating lymphocytes (TILs). Then, we analyzed the effect of IL-6 on NK cells through organoid culture and immunofluorescence. Finally, we explored the changes of related molecules and pathway might be involved.

Results

IL-6 may play an important role in the tumor microenvironment of early lung adenocarcinoma. Further research confirmed that the decrease of IL-6 in GGO tissue is consistent with the changes in NK cells, and there seems to be a correlation between these two phenomena.

Conclusion

The IL-6 expression status and NK cell levels of early lung adenocarcinoma as GGO are significantly reduced, and the stimulation of IL-6 can up-regulate or activate NK cells in GGO, providing new insights into the diagnosis and pathogenesis of early lung cancer.
Dosimetric Validation of a System to Treat Moving Tumors Using Scanned Ion Beams That Are Synchronized With Anatomical Motion
Authors: Lis Michelle , Newhauser Wayne , Donetti Marco , Wolf Moritz , Steinsberger Timo , Paz Athena , Graeff Christian
Published: September 2021

Purpose

The purpose of this study was to validate the dosimetric performance of scanned ion beam deliveries with motion-synchronization to heterogenous targets.

Methods

A 4D library of treatment plans, comprised of up to 10 3D sub-plans, was created with robust and conventional 4D optimization methods. Each sub-plan corresponded to one phase of periodic target motion. The plan libraries were delivered to a test phantom, comprising plastic slabs, dosimeters, and heterogenous phantoms. This phantom emulated range changes that occur when treating moving tumors. Similar treatment plans, but without motion synchronization, were also delivered to a test phantom with a stationary target and to a moving target; these were used to assess how the target motion degrades the quality of dose distributions and the extent to which motion synchronization can improve dosimetric quality. The accuracy of calculated dose distributions was verified by comparison with corresponding measurements. Comparisons utilized the gamma index analysis method. Plan quality was assessed based on conformity, dose coverage, overdose, and homogeneity values, each extracted from calculated dose distributions.

Results

High pass rates for the gamma index analysis confirmed that the methods used to calculate and reconstruct dose distributions were sufficiently accurate for the purposes of this study. Calculated and reconstructed dose distributions revealed that the motion-synchronized and static deliveries exhibited similar quality in terms of dose coverage, overdose, and homogeneity for all deliveries considered. Motion-synchronization substantially improved conformity in deliveries with moving targets. Importantly, measurements at multiple locations within the target also confirmed that the motion-synchronized delivery system satisfactorily compensated for changes in beam range caused by the phantom motion. Specifically, the overall planning and delivery approach achieved the desired dose distribution by avoiding range undershoots and overshoots caused by tumor motion.

Conclusions

We validated a dose delivery system that synchronizes the movement of the ion beam to that of a moving target in a test phantom. Measured and calculated dose distributions revealed that this system satisfactorily compensated for target motion in the presence of beam range changes due to target motion. The implication of this finding is that the prototype system is suitable for additional preclinical research studies, such as irregular anatomic motion.
Prognostic and Clinicopathological Value of Ki-67 in Melanoma: A Meta-Analysis
Authors: Liu Qixin , Peng Ziheng , Shen Liangfang , Shen Lin
Published: September 2021

Background

The prognostic and clinicopathological value of Ki-67 in melanoma is controversial. The purpose of this meta-analysis was to determine the prognostic role of Ki-67 in melanoma patients.

Materials and Methods

The PubMed, Cochrane Library, Web of Science, and Embase databases were searched systematically up to April 9, 2021. We calculated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the relationship between Ki-67 overexpression and survival outcomes. We also calculated the combined odds ratios (ORs) and 95% CIs to determine the relationship between Ki-67 expression levels and clinicopathologic parameters. All data were statistically analyzed by Stata 11.0.

Results

A total of 10 studies involving 929 patients were included in our meta-analysis. The pooled HR showed that Ki-67 overexpression was connected with poor overall survival rates (HR=2.92, 95% CI=2.17-3.91, p<0.000). However, there was no correlation between Ki-67 overexpression and the PFS (HR=0.999, 95% CI =0.958-1.041, P =0.958; I2 = 21.80%, P =0.258) or RFS (HR=1.14, 95% CI = 0.42-3.11, P =0.993; I2 = 85.00%, P =0.01) rates. Ki-67 expression levels were associated with tumor thickness, but not sex, location, ulceration or vascular invasion.

Conclusion

Ki-67 is a useful poor prognostic indicator for melanoma patients.
COVID-19 Pandemic and Reduced Physical Activity: Is There an Impact on Healthy and Asthmatic Children?
Authors: Ferrante Giuliana , Mollicone Desiree , Cazzato Salvatore , Lombardi Enrico , Pifferi Massimo , Turchetta Attilio , Tancredi Giancarlo , La Grutta Stefania
Published: September 2021

Physical activity (PA) has been seen to improve asthma symptoms, lung function, and quality of life, as well as to reduce airway inflammation and bronchial responsiveness. As a consequence of the COVID-19 pandemic, the minimal amount of PA recommended by the World Health Organization—i.e., about 60 min/day of moderate-to-high intensity—is difficult to achieve for many children, particularly those living in urban areas. Short-term changes in PA because of the COVID-19 pandemic may become habitual, increasing the risk of adverse asthma outcomes in children. Indeed, prolonged home confinement during the COVID-19 pandemic reduces PA levels and increases sedentary behaviors, possibly impairing immune system function and increasing susceptibility to inflammatory diseases. However, there is limited evidence regarding the effects of lockdown due to COVID-19 on PA and sedentary behaviors in asthmatic children. Given that children stay longer indoors, indoor air pollution represents a major issue to consider during home confinement. This narrative review aims to summarize the available evidence about the impact of decreased PA and increased sedentary behaviors on children with asthma during the COVID-19 pandemic. In addition, strategies for supporting PA in children with asthma during the COVID-19 pandemic are suggested, also looking at the issue of indoor air quality.
Schools as a Framework for COVID-19 Epidemiological Surveillance of Children in Catalonia, Spain: A Population-Based Study
Authors: Perramon Aida , Soriano-Arandes Antoni , Pino David , Lazcano Uxue , Andrés Cristina , Català Martí , Gatell Anna , Carulla Mireia , Canadell Dolors , Ricós Gemma , Riera-Bosch M. Teresa , Burgaya Silvia , Salvadó Olga , Cantero Javier , Vilà Mònica , Poblet Miriam , Sánchez Almudena , Ristol Anna M. , Serrano Pepe , Antón Andrés , Prats Clara , Soler-Palacin Pere
Published: September 2021

Objective: We describe and analyze the childhood (<18 years) COVID-19 incidence in Catalonia, Spain, during the first 36 weeks of the 2020-2021 school-year and to compare it with the incidence in adults.

Methods: Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests were obtained from the Catalan Agency for Quality and Health Assessment. Overall, 7,203,663 SARS-CoV-2 tests were performed, of which 491,819 were positive (6.8%). We collected epidemiological data including age-group incidence, diagnostic effort, and positivity rate per 100,000 population to analyze the relative results for these epidemiological characteristics.

Results: Despite a great diagnostic effort among children, with a difference of 1,154 tests per 100,000 population in relation to adults, the relative incidence of SARS-CoV-2 for <18 years was slightly lower than for the general population, and it increased with the age of the children. Additionally, positivity of SARS-CoV-2 in children (5.7%) was lower than in adults (7.2%), especially outside vacation periods, when children were attending school (4.9%).

Conclusions: A great diagnostic effort, including mass screening and systematic whole-group contact tracing when a positive was detected in the class group, was associated with childhood SARS-CoV-2 incidence and lower positivity rate in the 2020-2021 school year. Schools have been a key tool in epidemiological surveillance rather than being drivers of SARS-CoV-2 incidence in Catalonia, Spain.
Protective Effects of Inhibition of Mitochondrial Fission on Organ Function After Sepsis
Authors: Zhu Yu , Kuang Lei , Wu Yue , Deng Haoyue , She Han , Zhou Yuanqun , Zhang Jie , Liu Liangming , Li Tao
Published: September 2021

Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo. Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases.
Coupling Radiation Transport and Track-Structure Simulations: Strategy Based on Analytical Formulas Representing DNA Damage Yields
Authors: Kundrát Pavel , Friedland Werner , Ottolenghi Andrea , Baiocco Giorgio
Published: September 2021

Existing radiation codes for biomedical applications face the challenge of dealing with largely different spatial scales, from nanometer scales governing individual energy deposits to macroscopic scales of dose distributions in organs and tissues in radiotherapy. Event-by-event track-structure codes are needed to model energy deposition patterns at cellular and subcellular levels. In conjunction with DNA and chromatin models, they predict radiation-induced DNA damage and subsequent biological effects. Describing larger-scale effects is the realm of radiation transport codes and dose calculation algorithms. A coupling approach with a great potential consists in implementing into radiation transport codes the results of track-structure simulations captured by analytical formulas. This strategy allows extending existing transport codes to biologically relevant endpoints, without the need of developing dedicated modules and running new computationally expensive simulations. Depending on the codes used and questions addressed, alternative strategies can be adopted, reproducing DNA damage in dependence on different parameters extracted from the transport code, e.g., microdosimetric quantities, average linear energy transfer (LET), or particle energy. Recently, a comprehensive database on DNA damage induced by ions from hydrogen to neon, at energies from 0.5 GeV/u down to their stopping, has been created with PARTRAC biophysical simulations. The results have been captured as a function of average LET in the cell nucleus. However, the formulas are not applicable to slow particles beyond the Bragg peak, since these can have the same LET as faster particles but in narrower tracks, thus inducing different DNA damage patterns. Particle energy distinguishes these two cases. It is also more readily available than LET from some transport codes. Therefore, a set of new analytical functions are provided, describing how DNA damage depends on particle energy. The results complement the analysis of the PARTRAC database, widening its potential of application and use for implementation in transport codes.
Gardenoside Hinders Caspase-1-Mediated Hepatocyte Pyroptosis Through the CTCF/DPP4 Signaling Pathway
Authors: Shen Tian , Lei Tao , Chen Lin , Zhu Bing-Bing , Xu Bi-Lin , Zhang Cui-Ping , Wang Hong-Ping
Published: September 2021

Non-alcoholic fatty liver disease (NAFLD)is accompanied by typical inflammatory damage and cell death. As a pro-inflammatory form of cell death, pyroptosis participates in important pathological processes involved in NAFLD. Regulatory roles of both CCCTC-binding factor (CTCF) and dipeptidyl peptidase-4 (DPP4) have been reported in NAFLD, but it is still unclear whether the mechanism of action of gardenoside, a potential therapeutic for NAFLD, can be driven via these proteins. In this study, the direct interaction between CTCF and DPP4 was first confirmed by a dual-luciferase reporter assay system. Then, a cell model of NAFLD was established by induction with palmitic acid (PA) and lipopolysaccharide (LPS). A mouse NAFLD model was established, and the effect of gardenoside on both the cell and mouse models of NAFLD was also investigated. Increased lipid accumulation, NLRP3 inflammasome activation, and hepatocyte pyroptosis were recorded in NAFLD in vitro and in vivo. Gardenoside treatment effectively reduced the lipid accumulation, increased cell viability, reduced reactive oxygen species (ROS) generation, and attenuated pyroptosis and apoptosis in NAFLD in the in vitro and in vivo models. Alterations in these biological processes were evidenced by the decreased expression levels of several pro-pyroptotic markers including the NLR family, pyrin domain-containing 3 (NLRP3), apoptosis-related speckle-like protein (ASC), caspase-1 p20, Gasdermin D N-terminal domain (GSDMD-N), and IL-1β, along with simultaneously decreased CTCF and DPP4 levels. Importantly, CTCF silencing or DPP4 silencing exhibited effects similar to gardenoside treatment, while CTCF overexpression counteracted this trend, which indicated that CTCF might be a target responsible for gardenoside-induced alleviation of NAFLD, such therapeutic effects might be achieved through controlling the expression of the direct target of CTCF (DPP4) and several downstream molecules. In general, the current study provides a promising strategy for NAFLD treatment.
Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases
Authors: Vasileva Valeriia Y. , Sultanova Regina F. , Sudarikova Anastasia V. , Ilatovskaya Daria V.
Published: September 2021

Autosomal dominant (AD) and autosomal recessive (AR) polycystic kidney diseases (PKD) are severe multisystem genetic disorders characterized with formation and uncontrolled growth of fluid-filled cysts in the kidney, the spread of which eventually leads to the loss of renal function. Currently, there are no treatments for ARPKD, and tolvaptan is the only FDA-approved drug that alleviates the symptoms of ADPKD. However, tolvaptan has only a modest effect on disease progression, and its long-term use is associated with many side effects. Therefore, there is still a pressing need to better understand the fundamental mechanisms behind PKD development. This review highlights current knowledge about the fundamental aspects of PKD development (with a focus on ADPKD) including the PC1/PC2 pathways and cilia-associated mechanisms, major molecular cascades related to metabolism, mitochondrial bioenergetics, and systemic responses (hormonal status, levels of growth factors, immune system, and microbiome) that affect its progression. In addition, we discuss new information regarding non-pharmacological therapies, such as dietary restrictions, which can potentially alleviate PKD.
Cardiorespiratory Coordination During Exercise in Adults With Down Syndrome
Authors: Oviedo Guillermo R. , Garcia-Retortillo Sergi , Carbó-Carreté María , Guerra-Balic Myriam , Balagué Natàlia , Javierre Casimiro , Guàrdia-Olmos Joan
Published: September 2021

Introduction:Down syndrome (DS) is a chromosomal disorder affecting simultaneously cardiovascular and respiratory systems. There is no research studying the coupling between these systems during cardiorespiratory exercise testing in a population with DS. Cardiorespiratory coordination (CRC), evaluated through principal component analysis (PCA), measures the covariation of cardiorespiratory variables during exercise.

Objective:To investigate and compare CRC in adults with and without DS during maximal cardiorespiratory exercise testing.

Methods:Fifteen adults with DS and 15 adults without disabilities performed a maximal cardiorespiratory exercise test on a treadmill. First, the slope, and afterward the velocity was increased regularly until participants reached exhaustion. The time series of six selected cardiorespiratory variables [ventilation per minute, an expired fraction of O2, the expired fraction of CO2, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP)] were extracted for the analysis. The number of principal components (PCs), the first PC eigenvalues (PC1), and the information entropy were computed for each group (non-DS and DS) and compared using at-test or a Mann-Whitney U test.

Results:Two PCs in the non-DS group and three PCs in the DS group captured the variance of the studied cardiorespiratory variables. The formation of an additional PC in the DS group was the result of the shift of SBP and DBP from the PC1cluster of variables. Eigenvalues of PC1were higher in the non-DS (U= 30;p= 0.02;d= 1.47) than in the DS group, and the entropy measure was higher in the DS compared with the non-DS group (U= 37.5;p= 0.008;d= 0.70).

Conclusion:Adults with Down syndrome showed higher CRC dimensionality and a higher entropy measure than participants without disabilities. Both findings point toward a lower efficiency of the cardiorespiratory function during exercise in participants with DS. CRC appears as an alternative measure to investigate the cardiorespiratory function and its response to exercise in the DS population.
Distance Dependent Contribution of Ants to Pollination but Not Defense in a Dioecious, Ambophilous Gymnosperm
Authors: Aranda-Rickert Adriana , Torréns Javier , Yela Natalia I. , Brizuela María Magdalena , Di Stilio Verónica S.
Published: September 2021

Dioecious plants are obligate outcrossers with separate male and female individuals, which can result in decreased seed set with increasing distance between the sexes. Wind pollination is a common correlate of dioecy, yet combined wind and insect pollination (ambophily) could be advantageous in compensating for decreased pollen flow to isolated females. Dioecious, ambophilous gymnosperms Ephedra (Gnetales) secrete pollination drops (PDs) in female cones that capture airborne pollen and attract ants that feed on them. Plant sugary secretions commonly reward ants in exchange for indirect plant defense against herbivores, and more rarely for pollination. We conducted field experiments to investigate whether ants are pollinators and/or plant defenders of South American Ephedra triandra, and whether their contribution to seed set and seed cone protection varies with distance between female and male plants. We quantified pollen flow in the wind and assessed the effectiveness of ants as pollinators by investigating their relative contribution to seed set, and their visitation rate in female plants at increasing distance from the nearest male. Ants accounted for most insect visits to female cones of E. triandra, where they consumed PDs, and pollen load was larger on bigger ants without reduction in pollen viability. While wind pollination was the main contributor to seed set overall, the relative contribution of ants was distance dependent. Ant contribution to seed set was not significant at shorter distances, yet at the farthest distance from the nearest male (23 m), where 20 times less pollen reached females, ants enhanced seed set by 30% compared to plants depending solely on wind pollination. We found no evidence that ants contribute to plant defense by preventing seed cone damage. Our results suggest that, despite their short-range movements, ants can offset pollen limitation in isolated females of wind-pollinated plants with separate sexes. We propose that ants enhance plant reproductive success via targeted delivery of airborne pollen, through frequent contact with ovule tips while consuming PDs. Our study constitutes the first experimental quantification of distance-dependent contribution of ants to pollination and provides a working hypothesis for ambophily in other dioecious plants lacking pollinator reward in male plants.
A Theoretical Framework for a Hybrid View of the N400
Authors: Naumann Ralf , Petersen Wiebke
Published: September 2021

In this study, we present a novel theoretical account of the N400 event-related potential (ERP) component. Hybrid views interpret this ERP component in terms of two cognitive operations: (i) access of information, which is related to predictions (predictability component), and (ii) integration of information, which is related to plausibility (plausibility component). Though there is an empirical evidence for this view, what has been left open so far is how these two operations can be defined. In our approach, both components are related to categorization. The critical word and the argument position it is related to are associated with categories that have a graded structure. This graded structure is defined in terms of weights both on attributes and values of features belonging to a category. The weights, in turn, are defined using probability distributions. The predictability component is defined in terms of the information gain with respect to non mismatched features between the two categories. The plausibility component is defined as the difference in the degree of typicality between the two categories. Finally, the N400 amplitude is defined as a function of both components.
A Curriculum Integrating STEAM and Maker Education Promotes Pupils' Learning Motivation, Self-Efficacy, and Interdisciplinary Knowledge Acquisition
Authors: Jia Yangyang , Zhou Bing , Zheng Xudong
Published: September 2021

Contemporary society expects learners to synthesize large amounts of available information and take advantage of interdisciplinary knowledge to tackle complex, real-world issues. STEAM education aims to cultivate students' ability to solve such problems through interdisciplinary thinking but is often represented by courses that are merely disjointed arrays of school subjects. On the other hand, Maker education harnesses society's enthusiasm for technological innovation and creativity but overlooks the scientific principles that underpin these processes. This research presents a novel elementary school course informed by the interdisciplinary principles of STEAM, integrated with Maker's focus on technology and creativity. The course design also utilized engineering design as a meta-thematic framework. A total of 164 third-grade pupils participated in the research, with responses analyzed using descriptive statistical methods. The findings indicated that the integrated design of the course promoted pupils' learning motivation, self-efficacy, and acquisition of interdisciplinary knowledge. These effects were not gender-specific and demonstrate the potential applicability of a STEAM/Maker integrated approach to curriculum design in other settings.
Understanding ESL Teachers’ Agency in Their Early Years of Professional Development: A Three-Layered Triadic Reciprocity Framework
Authors: Huang Jing , Yip Jesse W. C.
Published: September 2021

Drawing upon the Triadic Reciprocity Framework, this longitudinal qualitative multiple-case study examined how three Hong Kong secondary English as a second language (ESL) teachers exercised their teacher agency to take control of their teaching and professional development. More specifically, the study aimed at exploring how teachers’ intentions and actions for the establishment of their professional identity were afforded and constrained by their workplaces. Findings reveal that these ESL teachers exercised different degrees of proactive, reactive, and passive agency. The four properties of human agency, i.e., intentionality, forethought, self-reactiveness, and self-reflectiveness, influenced the teachers’ proactive, reactive, and passive agency when they responded to personal, behavioral, and environmental determinants. The findings shed light on a three-layered Triadic Reciprocity framework on teacher agency and contributes to a systematic and comprehensive discussion about the various internal and external factors that might exert influences on agency of early career teachers. This study offers pedagogical implications for school teachers, school leaders, and policy makers in Hong Kong and beyond.