bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum proBDNF Is Associated With Changes in the Ketone Body β-Hydroxybutyrate and Shows Superior Repeatability Over Mature BDNF: Secondary Outcomes From a Cross-Over Trial in Healthy Older Adults
Authors: Norgren Jakob , Daniilidou Makrina , Kåreholt Ingemar , Sindi Shireen , Akenine Ulrika , Nordin Karin , Rosenborg Staffan , Ngandu Tiia , Kivipelto Miia , Sandebring-Matton Anna
Published: August 2021

Background: β-hydroxybutyrate (BHB) can upregulate brain-derived neurotrophic factor (BDNF) in mice, but little is known about the associations between BHB and BDNF in humans. The primary aim here was to investigate whether ketosis (i.e., raised BHB levels), induced by a ketogenic supplement, influences serum levels of mature BDNF (mBDNF) and its precursor proBDNF in healthy older adults. A secondary aim was to determine the intra-individual stability (repeatability) of those biomarkers, measured as intra-class correlation coefficients (ICC).

Method: Three of the arms in a 6-arm randomized cross-over trial were used for the current sub-study. Fifteen healthy volunteers, 65–75 y, 53% women, were tested once a week. Test oils, mixed in coffee and cream, were ingested after a 12-h fast. Labeled by their level of ketosis, the arms provided: sunflower oil (lowK); coconut oil (midK); caprylic acid + coconut oil (highK). Repeated blood samples were collected for 4 h after ingestion. Serum BDNF levels were analyzed for changes from baseline to 1, 2 and 4 h to compare the arms. Individual associations between BHB and BDNF were analyzed cross-sectionally and for a delayed response (changes in BHB 0–2 h to changes in BDNF at 0–4 h). ICC estimates were calculated from baseline levels from the three study days.

Results: proBDNF increased more in highK vs. lowK between 0 and 4 h (z-score: β = 0.25, 95% CI 0.07–0.44; p = 0.007). Individual change in BHB 0–2 h, predicted change in proBDNF 0–4 h, (β = 0.40, CI 0.12–0.67; p = 0.006). Change in mBDNF was lower in highK vs. lowK at 0–2 h (β = −0.88, CI −1.37 to −0.40; p < 0.001) and cumulatively 0–4 h (β = −1.01, CI −1.75 to −0.27; p = 0.01), but this could not be predicted by BHB levels. ICC was 0.96 (95% CI 0.92–0.99) for proBDNF, and 0.72 (CI 0.47–0.89) for mBDNF.

Conclusions: The findings support a link between changes in peripheral BHB and proBDNF in healthy older adults. For mBDNF, changes differed between arms but independent to BHB levels. Replication is warranted due to the small sample. Excellent repeatability encourages future investigations on proBDNF as a predictor of brain health.

Clinical Trial Registration:ClinicalTrials.gov, NCT03904433.
The Influence of Nutrition in Alzheimer's Disease: Neuroinflammation and the Microbiome vs. Transmissible Prion
Authors: Bello-Corral Laura , Sánchez-Valdeón Leticia , Casado-Verdejo Inés , Seco-Calvo Jesús Ángel , Antonio Fernández-Fernández Jesús , Nélida Fernández-Martínez María
Published: August 2021

Alzheimer's disease (AD) is a primary, progressive, neurodegenerative disorder. Many risk factors for the development of AD have been investigated, including nutrition. Although it has been proven that nutrition plays a role in AD, the precise mechanisms through which nutrition exerts its influence remain undefined. The object of this study is to address this issue by elucidating some of the mechanisms through which nutrition interacts with AD. This work is a qualitative systematic bibliographic review of the current literature searchable on various available databases, including PubMed, Web of Science, and Google Scholar. Our evidence comprises 31 articles selected after a systematic search process. Patients suffering with AD present a characteristic microbiome that promotes changes in microglia generating a proinflammatory state. Many similarities exist between AD and prion diseases, both in terms of symptoms and in the molecular mechanisms of pathogenesis. Changes in the composition of the gut microbiome due to dietary habits could be one of the environmental factors affecting the development of AD; however, this is probably not the only factor. Similarly, the mechanism for self-propagation of beta-amyloid seen in AD is similar to that seen in prions.
Machine Learning-Based Analysis of Magnetic Resonance Radiomics for the Classification of Gliosarcoma and Glioblastoma
Authors: Qian Zenghui , Zhang Lingling , Hu Jie , Chen Shuguang , Chen Hongyan , Shen Huicong , Zheng Fei , Zang Yuying , Chen Xuzhu
Published: August 2021

Objective

To identify optimal machine-learning methods for the radiomics-based differentiation of gliosarcoma (GSM) from glioblastoma (GBM).

Materials and Methods

This retrospective study analyzed cerebral magnetic resonance imaging (MRI) data of 83 patients with pathologically diagnosed GSM (58 men, 25 women; mean age, 50.5 ± 12.9 years; range, 16-77 years) and 100 patients with GBM (58 men, 42 women; mean age, 53.4 ± 14.1 years; range, 12-77 years) and divided them into a training and validation set randomly. Radiomics features were extracted from the tumor mass and peritumoral edema. Three feature selection and classification methods were evaluated in terms of their performance in distinguishing GSM and GBM: the least absolute shrinkage and selection operator (LASSO), Relief, and Random Forest (RF); and adaboost classifier (Ada), support vector machine (SVM), and RF; respectively. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of each method were analyzed.

Results

Based on tumor mass features, the selection method LASSO + classifier SVM was found to feature the highest AUC (0.85) and ACC (0.77) in the validation set, followed by Relief + RF (AUC = 0.84, ACC = 0.72) and LASSO + RF (AUC = 0.82, ACC = 0.75). Based on peritumoral edema features, Relief + SVM was found to have the highest AUC (0.78) and ACC (0.73) in the validation set. Regardless of the method, tumor mass features significantly outperformed peritumoral edema features in the differentiation of GSM from GBM (P < 0.05). Furthermore, the sensitivity, specificity, and accuracy of the best radiomics model were superior to those obtained by the neuroradiologists.

Conclusion

Our radiomics study identified the selection method LASSO combined with the classifier SVM as the optimal method for differentiating GSM from GBM based on tumor mass features.
Caveolin-1, a Key Mediator Across Multiple Pathways in Glioblastoma and an Independent Negative Biomarker of Patient Survival
Authors: Moriconi Chiara , Civita Prospero , Neto Catia , Pilkington Geoffrey J. , Gumbleton Mark
Published: August 2021

Glioblastoma (GB) remains an aggressive malignancy with an extremely poor prognosis. Discovering new candidate drug targets for GB remains an unmet medical need. Caveolin-1 (Cav-1) has been shown to act variously as both a tumour suppressor and tumour promoter in many cancers. The implications of Cav-1 expression in GB remains poorly understood. Using clinical and genomic databases we examined the relationship between tumour Cav-1 gene expression (including its spatial distribution) and clinical pathological parameters of the GB tumour and survival probability in a TCGA cohort (n=155) and CGGA cohort (n=220) of GB patients. High expression of Cav-1 represented a significant independent predictor of shortened survival (HR = 2.985, 5.1vs14.9 months) with a greater statistically significant impact in female patients and in the Proneural and Mesenchymal GB subtypes. High Cav-1 expression correlated with other factors associated with poor prognosis: IDH w/t status, high histological tumour grade and low KPS score. A total of 4879 differentially expressed genes (DEGs) in the GB tumour were found to correlate with Cav-1 expression (either positively or negatively). Pathway enrichment analysis highlighted an over-representation of these DEGs to certain biological pathways. Focusing on those that lie within a framework of epithelial to mesenchymal transition and tumour cell migration and invasion we identified 27 of these DEGs. We then examined the prognostic value of Cav-1 when used in combination with any of these 27 genes and identified a subset of combinations (with Cav-1) indicative of co-operative synergistic mechanisms of action. Overall, the work has confirmed Cav-1 can serve as an independent prognostic marker in GB, but also augment prognosis when used in combination with a panel of biomarkers or clinicopathologic parameters. Moreover, Cav-1 appears to be linked to many signalling entities within the GB tumour and as such this work begins to substantiate Cav-1 or its associated signalling partners as candidate target for GB new drug discovery.
Comprehensive Pan-Cancer Analysis and the Regulatory Mechanism of ASF1B, a Gene Associated With Thyroid Cancer Prognosis in the Tumor Micro-Environment
Authors: Ma Jing , Han Wei , Lu Kai
Published: August 2021

Background

The incidence of thyroid cancer, whose local recurrence and metastasis lead to death, has always been high and the pathogenesis of papillary thyroid carcinoma (PTC) has not been clearly elucidated. Therefore, the research for more accurate prognosis-related predictive biomarkers is imminent, and a key gene can often be a prognostic marker for multiple tumors.

Methods

Gene expression profiles of various cancers in the TCGA and GTEx databases were downloaded, and genes significantly associated with the prognosis of THCA were identified by combining differential analysis with survival analysis. Then, a series of bioinformatics tools and methods were used to analyze the expression of the gene in each cancer and the correlation of each expression with prognosis, tumor immune microenvironment, immune neoantigens, immune checkpoints, DNA repair genes, and methyltransferases respectively. The possible biological mechanisms were also investigated by GSEA enrichment analysis.

Results

656 differentially expressed genes were identified from two datasets and 960 DEGs that were associated with disease-free survival in THCA patients were screened via survival analysis. The former and the latter were crossed to obtain 7 key genes, and the gene with the highest risk factor, ASF1B, was selected for this study. Differential analysis of multiple databases showed that ASF1B was commonly and highly expressed in pan-cancer. Survival analysis showed that high ASF1B expression was significantly associated with poor patient prognosis in multiple cancers. In addition, ASF1B expression levels were found to be associated with tumor immune infiltration in THCA, KIRC, LGG, and LIHC, and with tumor microenvironment in BRCA, LUSC, STAD, UCEC, and KIRC. Further analysis of the relationship between ASF1B expression and immune checker gene expression suggested that ASF1B may regulate tumor immune patterns in most tumors by regulating the expression levels of specific immune checker genes. Finally, GSEA enrichment analysis showed that ASF1B high expression was mainly enriched in cell cycle, MTORC1 signaling system, E2F targets, and G2M checkpoints pathways.

Conclusions

ASF1B may be an independent prognostic marker for predicting the prognosis of THCA patients. The pan-cancer analysis suggested that ASF1B may play an important role in the tumor micro-environment and tumor immunity and it has the potential of serving as a predictive biomarker for multiple cancers.
The Association Between Single-Child Status and Risk of Abdominal Obesity: Result From a Cross-Sectional Study of China
Authors: Gao Di , Li Yanhui , Yang Zhaogeng , Ma Ying , Chen Manman , Dong Yanhui , Zou Zhiyong , Ma Jun
Published: August 2021

Background:Obesity has become a serious problem threatening the health of children and adolescents, and China's one-child policy has affected family structure and parenting practice, which may result in several adverse health outcomes. The present study aims to investigate the association between single-child status and the risk of abdominal obesity in Chinese adolescents and also to compare the differences in the risk of unideal energy-related behaviors.

Methods:Data were obtained from a school-based cross-sectional survey conducted in seven provinces of China, in 2012. A total of 31,291 students aged 7–17 years were recruited in this study. Anthropometric measurements were conducted to assess height and waist circumference, and questionnaires were used to obtain information of single-child status, parental educational attainment, parental weight status, and offspring energy-related behaviors. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (95% CI) of single-child status and odds of childhood abdominal obesity and energy-related behaviors.

Results:The prevalence of abdominal obesity was 18.2% in single children, which was higher than that of non-single children (13.7%). The prevalence was also higher in single children in different sex and residence subgroups. Logistic regression models showed that single children had 1.33 times (OR: 1.33, 95% CI: 1.24–1.43,P< 0.001) higher odds of abdominal obesity compared to non-single children. Single children had 1.08 times higher odds of physical inactivity (OR: 1.08, 95% CI: 1.03–1.14,P= 0.004), 1.13 times higher odds of excessive sugar-sweetened beverages (SSBs) consumption (OR: 1.13, 95% CI: 1.05–1.23,P= 0.002), and 1.08 times more likely to eat out (OR: 1.08, 95% CI: 1.02–1.13,P= 0.006). Those associations were more remarkable in single girls.

Conclusion:Being a single child may be associated with a higher odds of childhood abdominal obesity and unhealthy energy-related behaviors. Future interventions and strategies to prevent abdominal obesity should focus on this high-risk population.
Treating Children With Advanced Rheumatic Heart Disease in Sub-Saharan Africa: The NGO EMERGENCY's Project at the Salam Centre for Cardiac Surgery in Sudan
Authors: Miccio Rossella , Quattrociocchi Maria , Valgoi Lorenzo , Chatenoud Liliane , Lentini Salvatore , Giovanella Elena , Rolla Luca , Erba Nicoletta , Gatti Sofia , Rocchi Daniela , Saad Manahel Badr , Salvati Alessandro , Langer Martin , Portella Gina , Strada Gino
Published: August 2021

Rheumatic heart disease is endemic in Sub-Saharan Africa and while efforts are under way to boost prophylaxis and early diagnosis, access to cardiac surgery is rarely affordable. In this article, we report on a humanitarian project by the NGO EMERGENCY, to build and run the Salam Centre for Cardiac Surgery in Sudan. This hospital is a center of excellence offering free-of-charge, high-quality treatment to patients needing open-heart surgery for advanced rheumatic and congenital heart disease. Since it opened in 2007, more than 8,000 patients have undergone surgery there; most of them Sudanese, but ~20% were admitted from other countries, an example of inter-African cooperation. The program is not limited to surgical procedures. It guarantees long-term follow-up and anticoagulant treatment, where necessary. By way of example, we report clinical features and outcome data for the pediatric cohort: 1,318 children under the age of 15, operated on for advanced rheumatic heart disease between 2007 and 2019. The overall 5-year survival rate was 85.0% (95% CI 82.7–87.3). The outcomes for patients with mitral valves repaired and with mitral valves replaced are not statistically different. Nevertheless, observing the trend of patients undergoing valve repair, a better outcome for this category might be assumed. RHD in children is an indicator of poor socio-economic conditions and an inadequate health system, which clearly will not be cured by cardiac surgery alone. Nevertheless, the results achieved by EMERGENCY, with the crucial involvement and participation of the Sudanese government over the years, show that building a hospital, introducing free cardiac surgery, and offering long-term post-operative care may help spread belief in positive change in the future.
The Preventive Role of Hydrogen-Rich Water in Thioacetamide-Induced Cholangiofibrosis in Rat Assessed by Automated Histological Classification
Authors: Li Chaofu , Zhao Xing , Gu Xiaoqiang , Chen Ying , Yu Guanzhen
Published: August 2021

Background: Cholangiofibrosis is a controversial intrahepatic cholangial lesion that precedes the development of cholangiocarcinoma. Here, we demonstrate that molecular hydrogen (H2) can be used to effectively prevent cholangiofibrosis.

Methods: The safety and quality of life (QOL) of rats was firstly evaluated. H2 was administered to rats subjected to thioacetamide (TAA)-induced cholangiofibrosis throughout the whole process. Then, rats were administrated with TAA for 3 months and then followed by H2 intervention. Rat livers were harvested and assessed by light microscopy and convolutional neural network. RNA-seq was performed to analyze the genetic changes in these animal models.

Results: Continuous use of H2-rich water was safe and improved QOL.The incidence and average number of cholangiofibrosis in the liver were higher in the TAA group (100%, 12.0 ± 10.07) than that in the H2 group (57.1%, 2.86 ± 5.43). The AI algorithm revealed higher Alesion/Aliver in the TAA group (19.6% ± 9.01) than that in the H2 group (7.54% ± 11.0). RNA-seq analysis revealed that H2 results in a decline in glycolysis. Moreover, in the third experiment, the incidence of microscopic or suspicious tumors and the ratio of liver lesions was decreased after long-term use of H2 (12.5%, 0.57% ± 0.45) compared with untreated group (100%, 0.98% ± 0.73). A number of intestinal microbiota was changed after H2 usage, including clostridiaceae_1, ruminococcus, turicibacter, coriobacteriales, actinobacteria, and firmicutes_bacterium.

Conclusion: Hydrogen-rich water protects against liver injury and cholangiofibrosis and improved quality of life partially through regulating the composition of intestinal flora.
Medicinal Animals and Plants as Alternative and Complementary Medicine in Southern Regions of Khyber Pakhtunkhwa, Pakistan
Authors: Mussarat Sakina , Ali Rehman , Ali Shandana , Mothana Ramzi A. , Ullah Riaz , Adnan Muhammad
Published: August 2021

Background: Local communities use animals and plants as common traditional therapies for various diseases. The study aimed to document animals and animal-plant mixture recipes that are used as alternative and complementary medicine in southern regions of Khyber Pakhtunkhwa, Pakistan.

Methods: The data were collected (2017–2018) in three remote areas (Dera Ismail Khan, Bannu, and Lakki Marwat) through questionnaires and face-to-face interviews with local inhabitants. Data on ethnomedicinal uses and cultural values of animal products or parts and their mixture with plants were analyzed using various indices such as frequency of citation (FC), informant consensus (FIC), and fidelity level (FL) to find the highly preferred species in the area.

Results: A total of 185 informants (117 females and 68 males) were interviewed. The study documented 32 animal species, vertebrates (n = 24) and invertebrates (n = 8), for curing 37 types of diseases. Mammals (n = 13) were among the most commonly utilized species followed by birds (n = 8), arthropods (n = 7), reptiles (n = 2), and fishes and annelids (n = 1 each). Among the reported animals, Herpestes edwardsi (mongoose), Macaca mulatta (monkey), Labeo rohita (rohu), Oryctolagus cuniculus (rabbit), and Streptopelia decaocto (dove) were the newly reported species used as alternative medicine. The meat of Capra hircus (goat), monkey, and rabbit was used to treat chronic diseases such as hepatitis C, cancer, epilepsy, and asthma. A total of 17 plants belonging to 15 botanical families were used in combination with animal parts/products. The commonly used families were Piperaceae (31%) followed by Apiaceae (27%). The notable plant species in combination with animal products were Curcuma longa, Piper nigrum, Coriandrum sativum, Brassica rapa, and Phoenix dactylifera. Seeds were the highest used part in animal-plant mixture recipes. Gallus gallus (chicken) and Columba livia (pigeon) secured the highest (FC = 28) and (FL = 80%), respectively. FIC results had shown the highest degree of consensus for general body weakness (FIC = 0.88) and pyrexia (FIC = 0.86).

Conclusion: Our findings suggest that local communities in the southern regions of Khyber Pakhtunkhwa have substantial knowledge about the formulation of ethnomedicines from both flora and fauna that need urgent documentation to avoid eroding and for conservational purposes. The newly reported phytozootherapeutic recipes and animal species can potentially be a source of pharmacologically active constituents and should be checked experimentally for further confirmation.
Traditionally Used Plants in the Treatment of Diabetes Mellitus: Screening for Uptake Inhibition of Glucose and Fructose in the Caco2-Cell Model
Authors: Schreck Katharina , Melzig Matthias F.
Published: August 2021

The traditional use of plants and their preparations in the treatment of diseases as a first medication in the past centuries indicates the presence of active components for specific targets in the natural material. Many of the tested plants in this study have been traditionally used in the treatment of Diabetes mellitus type 2 and associated symptoms in different cultural areas. Additionally, hypoglycemic effects, such as a decrease in blood glucose concentration, have been demonstrated in vivo for these plants. In order to determine the mode of action, the plants were prepared as methanolic and aqueous extracts and tested for their effects on intestinal glucose and fructose absorption in Caco2 cells. The results of this screening showed significant and reproducible inhibition of glucose uptake between 40 and 80% by methanolic extracts made from the fruits of Aronia melanocarpa, Cornus officinalis, Crataegus pinnatifida, Lycium chinense, and Vaccinium myrtillus; the leaves of Brassica oleracea, Juglans regia, and Peumus boldus; and the roots of Adenophora triphylla. Furthermore, glucose uptake was inhibited between 50 and 70% by aqueous extracts made from the bark of Eucommia ulmoides and the fruit skin of Malus domestica. The methanolic extracts of Juglans regia and Peumus boldus inhibited the fructose transport between 30 and 40% in Caco2 cells as well. These findings can be considered as fundamental work for further research regarding the treatment of obesity-correlated diseases, such as Diabetes mellitus type 2.
Comparative Toxicity Assessment of Kratom Decoction, Mitragynine and Speciociliatine Versus Morphine on Zebrafish (Danio rerio) Embryos
Authors: Damodaran Thenmoly , Chear Nelson Jeng-Yeou , Murugaiyah Vikneswaran , Mordi Mohd Nizam , Ramanathan Surash
Published: August 2021

Background: Kratom (Mitragyna speciosa Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use.

Aim of the study: The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model.

Methods: The zebrafish embryos were exposed to kratom decoction (1,000–62.5 μg/ml), mitragynine, speciociliatine, and morphine (100–3.125 μg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively.

Results: Kratom decoction at a concentration range of ≥500 μg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 μg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos.

Conclusion: Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.
Heat Transfer Analysis of 3-D Viscoelastic Nanofluid Flow Over a Convectively Heated Porous Riga Plate with Cattaneo-Christov Double Flux
Authors: Loganathan K. , Alessa Nazek , Kayikci Safak
Published: August 2021

The impact of heat-absorbing viscoelastic nanofluidic flow along with a convectively heated porous Riga plate with Cattaneo-Christov double flux was analytically investigated. The Buongiorno model nanofluid was implemented with the diversity of Brownian motion and thermophoresis. Making use of the transformations; the PDE systems are altered into an ODE system. We use the homotopy analysis method to solve these systems analytically. The reaction of the apposite parameters on fluid velocity, fluid temperature, nanoparticle volume fraction skin friction coefficients (SFC), local Nusselt number and local Sherwood number are shown with vividly explicit details. It is found that the fluid velocities reflect a declining nature for the development of viscoelastic and porosity parameters. The liquid heat becomes rich when escalating the radiation parameter. In addition, the nanoparticle volume fraction displays a declining nature towards the higher amount of thermophoresis parameter, whereas the inverse trend was obtained for the Brownian motion parameter. We also found that the fluid temperature is increased in viscoelastic nanofluid compared to the viscous nanofluid. When we change the fluid nature from heat absorption to heat generation, the liquid temperature also rises. In addition, the fluid heat is suppressed when we change the flow medium from a stationary plate to a Riga plate for heat absorption/generation cases.
Information Cascades Prediction With Graph Attention
Authors: Chen Zhihao , Wei Jingjing , Liang Shaobin , Cai Tiecheng , Liao Xiangwen
Published: August 2021

The cascades prediction aims to predict the possible information diffusion path in the future based on cascades of the social network. Recently, the existing researches based on deep learning have achieved remarkable results, which indicates the great potential to support cascade prediction task. However, most prior arts only considered either cascade features or user relationship network to predict cascade, which leads to the performance limitation because of the lack of unified modeling for the potential relationship between them. To that end, in this paper, we propose a recurrent neural network model with graph attention mechanism, which constructs a seq2seq framework to learn the spatial-temporal cascade features. Specifically, for user spatial feature, we learn potential relationship among users based on social network through graph attention network. Then, for temporal feature, a recurrent neural network is built to learn their structural context in several different time intervals based on timestamp with a time-decay attention. Finally, we predict the next user with the latest cascade representation which obtained by above method. Experimental results on two real-world datasets show that our model achieves better performance than the baselines on the both evaluation metrics of HITS and mean average precision.
Influence of Exercise on Exhausted and Senescent T Cells: A Systematic Review
Authors: Donovan Thomasina , Bain Amanda L. , Tu Wenjuan , Pyne David B. , Rao Sudha
Published: August 2021

The impaired effector function of exhausted and senescent T cells is implicated in cancer progression and inadequate vaccine responses. Exercise has been shown to improve cancer therapy and vaccine efficacy, most likely by improving immune function. However, given inconsistent terminology and definitions, the interactions between exercise and exhausted and senescent T cells remain unclear. We therefore performed a systematic review to investigate the effect of exercise on senescent and exhausted CD8+T cell populations clearly defined by protein surface markers. Thirty articles were included, with the majority (n= 24) reporting senescent T cell populations defined according to a variety of surface markers. Repeated exercise was shown to be beneficial through limiting the accumulation of senescent and exhausted CD8+T cells. This outcome is likely related to exercise-induced preferential mobilization of senescent T cells promoting apoptosis in the peripheral blood compartment. Future studies need to determine the clinical relevance of this effect in cancer prevention and vaccine efficacy. Data regarding exercise and exhausted T cells are limited due to a lack of available high-quality studies. Future studies require the control of confounding variables such as sex and cytomegalovirus (CMV) status, and consistent definitions of exhausted and senescent T cell populations to improve comparisons between studies and interventions.
Automated Classification of Whole Body Plethysmography Waveforms to Quantify Breathing Patterns
Authors: Sunshine Michael D. , Fuller David D.
Published: August 2021

Whole body plethysmography (WBP) monitors respiratory rate and depth but conventional analysis fails to capture the diversity of waveforms. Our first purpose was to develop a waveform cluster analysis method for quantifying dynamic changes in respiratory waveforms. WBP data, from adult Sprague-Dawley rats, were sorted into time domains and principle component analysis was used for hierarchical clustering. The clustering method effectively sorted waveforms into categories including sniffing, tidal breaths of varying duration, and augmented breaths (sighs). We next used this clustering method to quantify breathing after opioid (fentanyl) overdose and treatment with ampakine CX1942, an allosteric modulator of AMPA receptors. Fentanyl caused the expected decrease in breathing, but our cluster analysis revealed changes in the temporal appearance of inspiratory efforts. Ampakine CX1942 treatment shifted respiratory waveforms toward baseline values. We conclude that this method allows for rapid assessment of breathing patterns across extended data recordings. Expanding analyses to include larger portions of recorded WBP data may provide insight on how breathing is affected by disease or therapy.
The Overlooked Biomechanical Role of the Clasping Leaf Sheath in Wheat Stalk Lodging
Authors: Cornwall Joseph , Stubbs Christopher J. , McMahan Christopher S. , Robertson Daniel J.
Published: August 2021

The biomechanical role of the clasping leaf sheath in stalk lodging events has been historically understudied. Results from this study indicate that in some instances the leaf sheath plays an even larger role in reinforcing wheat against stalk lodging than the stem itself. Interestingly, it appears the leaf sheath does not resist bending loads by merely adding more material to the stalk (i.e., increasing the effective diameter). The radial preload of the leaf sheath on the stem, the friction between the sheath and the stem and several other complex biomechanical factors may contribute to increasing the stalk bending strength and stalk flexural rigidity of wheat. Results demonstrated that removal of the leaf sheath induces alternate failure patterns in wheat stalks. In summary the biomechanical role of the leaf sheath is complex and has yet to be fully elucidated. Many future studies are needed to develop high throughput phenotyping methodologies and to determine the genetic underpinnings of the clasping leaf sheath and its relation to stalk lodging resistance. Research in this area is expected to improve the lodging resistance of wheat.
Global Identification and Systematic Analysis of Lysine Malonylation in Maize (Zea mays L.)
Authors: Xu Min , Tian Xiaomin , Ku Tingting , Wang Guangyuan , Zhang Enying
Published: August 2021

Lysine malonylation is a kind of post-translational modifications (PTMs) discovered in recent years, which plays an important regulatory role in plants. Maize (Zea mays L.) is a major global cereal crop. Immunoblotting revealed that maize was rich in malonylated proteins. We therefore performed a qualitative malonylome analysis to globally identify malonylated proteins in maize. In total, 1,722 uniquely malonylated lysine residues were obtained in 810 proteins. The modified proteins were involved in various biological processes such as photosynthesis, ribosome and oxidative phosphorylation. Notably, a large proportion of the modified proteins (45%) were located in chloroplast. Further functional analysis revealed that 30 proteins in photosynthesis and 15 key enzymes in the Calvin cycle were malonylated, suggesting an indispensable regulatory role of malonylation in photosynthesis and carbon fixation. This work represents the first comprehensive survey of malonylome in maize and provides an important resource for exploring the function of lysine malonylation in physiological regulation of maize.
Climate Governance and Agriculture in Southeast Asia: Learning From a Polycentric Approach
Authors: Fasting Siw , Bacudo Imelda , Damen Beau , Dinesh Dhanush
Published: August 2021

The global climate governance framework will need to empower a wide range of groups representing different geopolitical and sector-specific interests to engage in climate action. Learning from polycentric governance approaches could provide insight on how to foster more inclusive engagement and more effective outcomes from global efforts to fight climate change. The Paris Agreement has opened up room for this type of bottom-up, polycentric governance and new attention to important issues such as agriculture. The Association of Southeast Asian Nations Climate Resilience Network (ASEAN-CRN) is an example of a polycentric system to enhance resilience and adapt to climate change. The ASEAN Negotiating Group on Agriculture (ANGA) enables the region’s agriculture sector to shape global climate governance frameworks. The case of ANGA highlights that opening up space for polycentric systems can foster climate action in relevant sectors. Supporting regions to navigate UNFCCC processes can further enable polycentric systems, enhancing climate resilience and adaptation.
Generalization and False Memory in an Acquired Equivalence Paradigm: The Influence of Physical Resemblance Across Related Episodes
Authors: Bowman Caitlin R. , de Araujo Sanchez Maria-Alejandra , Hou William , Rubin Sarina , Zeithamova Dagmar
Published: August 2021

The ability to make inferences about related experiences is an important function of memory that allows individuals to build generalizable knowledge. In some cases, however, making inferences may lead to false memories when individuals misremember inferred information as having been observed. One factor that is known to increase the prevalence of false memories is the physical resemblance between new and old information. The extent to which physical resemblance has parallel effects on generalization and memory for the source of inferred associations is not known. To investigate the parallels between memory generalization and false memories, we conducted three experiments using an acquired equivalence paradigm and manipulated physical resemblance between items that made up related experiences. The three experiments showed increased generalization for higher levels of resemblance. Recognition and source memory judgments revealed that high rates of generalization were not always accompanied by high rates of false memories. Thus, physical resemblance across episodes may promote generalization with or without a trade-off in terms of impeding memory specificity.
A Developmental Embodied Choice Perspective Explains the Development of Numerical Choices
Authors: Michirev Alexej , Musculus Lisa , Raab Markus
Published: August 2021

The goal of this paper is to explore how an embodied view can redirect our understanding of decision making. To achieve this goal, we contribute a developmental embodied choice perspective. Our perspective integrates embodiment and bounded rationality from a developmental view in which the body provides cues that are used in abstract choices. Hereby, the cues evolve with the body that is not static and changes through development. To demonstrate the body’s involvement in abstract choices, we will consider choices in numerical settings in which the body is not necessarily needed for the solution. For this, we consider the magnitude-judgment task in which one has to choose the larger of two magnitudes. In a nutshell, our perspective will pinpoint how the concept of embodied choices can explain the development of numerical choices.
An Ecological Study of a Universal Employee Depression Awareness and Stigma Reduction Intervention: “Right Direction”
Authors: Doty Benjamin , Grzenda Adrienne , Hwang Seungyoung , Godar Sean , Gruttadaro Darcy , Hauge Kimberly A. , Sherman Bruce , Clarke Diana E.
Published: August 2021

Objective: Right Direction (RD) was a component of a universal employee wellness program implemented in 2014 at Kent State University (KSU) to increase employees' awareness of depression, reduce mental health stigma, and encourage help-seeking behaviors to promote mental health. We explored changes in mental health care utilization before and after implementation of RD.

Methods: KSU Human Resources census and service use data were used to identify the study cohort and examine the study objectives. A pre-post design was used to explore changes in mental health utilization among KSU employees before and after RD. Three post-intervention periods were examined. A generalized linear mixed model approach was used for logistic regression analysis between each outcome of interest and intervention period, adjusted by age and sex. Logit differences were calculated for post-intervention periods compared to the pre-intervention period.

Results: Compared to the pre-intervention period, the predicted proportion of employees seeking treatment for depression and anxiety increased in the first post-intervention period (OR = 2.14, 95% Confidence Interval [CI] = 1.37–3.34), then declined. Outpatient psychiatric treatment utilization increased significantly in the first two post-intervention periods (OR =1.89, 95% CI = 1.23–2.89; OR = 1.75, 95% CI = 1.11–2.76). No difference was noted in inpatient psychiatric treatment utilization across post-intervention periods. Unlike prescription for anxiolytic prescriptions, receipt of antidepressant prescriptions increased in the second (OR = 2.25, 95% CI = 1.56–3.27) and third (OR = 2.16, 95% CI = 1.46–3.20) post-intervention periods.

Conclusions: Effects of RD may be realized over the long-term with follow-up enhancements such as workshops/informational sessions on mindfulness, stress management, resiliency training, and self-acceptance.
Older Adults and the COVID-19 Pandemic, What About the Oldest Old? The PACOVID Population-Based Survey
Authors: Hernández-Ruiz Virgilio , Meillon Céline , Avila-Funes José-Alberto , Bergua Valérie , Dartigues Jean-François , Koleck Michèle , Letenneur Luc , Ouvrard Camille , Pérès Karine , Rascle Nicole , Tabue-Teguo Maturin , Amieva Hélène
Published: August 2021

Introduction: The literature draws a mitigated picture of the psychosocial effects of the lockdown in older adults. However, the studies conducted so far are mainly based on web surveys which may involve selection bias. The PACOVID survey relies on a population-based design and addresses the attitudes, psychological and social experiences of the oldest old regarding the pandemic and lockdown and their impact.

Material and Methods: Cross-sectional phone survey involving 677 persons. Baseline report on attitudes, psychological, and social experiences of the oldest old, regarding the pandemic and lockdown measures.

Results: The mean age was 87.53 (SD 5.19). About 46% were living alone during the lockdown. Concerning difficulties, “none” was the most frequent answer (35.6%). For questions addressing how often they had felt sad, depressed, or lonely (CESD-scale), the most frequent answers were “never/very rarely” (58.7, 76.6, 60.8%) and 27.1% had anxious symptomatology (STAI scale). Most (92.9%) felt socially supported. Engaging in leisure activities was the most frequent coping strategy, and for numerous participants the lockdown did not represent much of a change in terms of daily routine. A very good knowledge and awareness of COVID-19 and the safety measures was observed. Comparisons with measures collected before the pandemic showed low changes in subjective health and the CES-D questions.

Discussion: With a methodological design limiting selection bias, our results claim for a weakened psychosocial impact even though the participants are concerned and aware of the pandemic issues. These results highlight the resources and resilience abilities of older persons including in advancing age.
Assessing Student Perceptions of a Norwegian University's COVID-19 Response Strategy: A Cross-Sectional Study
Authors: Vande Velde Fiona , Hamed Ahmed , Lange Joakim Slinning , Sælid Turid , Bastien Sheri
Published: August 2021

Aim: This study aims to investigate Norwegian students' perceptions toward a higher education institution (HEI)'s COVID-19 response strategy, differentiating between three behavioral techniques: informing (i. e., email updates about COVID-19), nudging (i.e., visual cues as reminders), and creating novel opportunities (i.e., provision of antibacterial dispensers). In addition, the study assesses to what extent these perceptions are influenced by COVID-19 related psychological factors: risk perception; attitudes toward infection prevention and control (IPC) behaviors; perceived behavior control; institutional trust.

Methods: A cross-sectional online survey was conducted among a student population. The survey was developed to evaluate the HEI's response strategy, and distinct perceptions of COVID-19 and related practices. Structural equation modeling (SEM) was applied to estimate the effect of the psychological factors on the attitude toward different behavioral techniques.

Results: Creating novel opportunities was perceived most positively from the students, secondly, informing the students through email updates about COVID-19, finally, reminders through visual cues. Institutional trust presented the largest positive effect on informing the students through email updates, while no effect was measured for reminders. Attitudes toward IPC behaviors showed the strongest effect on students' perceptions of new opportunities and reminders, whereas providing email updates about COVID-19 is less affected by pre-existing perceptions.

Conclusions: A host of factors such as institutional trust, and perceptions concerning IPC measures and risk severity, influence students' perceptions of different behavior change techniques. This type of knowledge can contribute to understanding how perceptions can impact acceptance and adoption of specific preventive measures within a pandemic response. An assessment as such may result in more ethical and relevant future efforts.
AntAlate—A Multi-Agent Autonomy Framework
Authors: Dovrat David , Bruckstein Alfred M.
Published: August 2021

AntAlate is a software framework for Unmanned Aerial Vehicle (UAV) autonomy, designed to streamline and facilitate the work of application developers, particularly in deployment of Multi-Agent Robotic Systems (MARS). We created AntAlate in order to bring our research in the field of multi-agent systems from theoretical results to both advanced simulations and to real-life demonstrations. Creating a framework capable of catering to MARS applications requires support for distributed, decentralized, control using local sensing, performed autonomously by groups of identical anonymous agents. Though mainly interested in the emergent behavior of the system as a whole, we focused on the single agent and created a framework suitable for a system of systems approach, while minimizing the hardware requirements of the single agent. Global observers or even a centralized control can be added on top of AntAlate, but the framework does not require a global actor to finalize an application. The same applies to a human in the loop, and fully autonomous UAV applications can be written in as straightforward a way as can semi-autonomous applications. In this paper we describe the AntAlate framework and demonstrate its utility and versatility.
Perturbation-Based Balance Training Using Repeated Trips on a Walkway vs. Belt Accelerations on a Treadmill: A Cross-Over Randomised Controlled Trial in Community-Dwelling Older Adults
Authors: Song Patrick Y. H. , Sturnieks Daina L. , Davis Michael K. , Lord Stephen R. , Okubo Yoshiro
Published: August 2021

Background: Walkway and treadmill induced trips have contrasting advantages, for instance walkway trips have high-ecological validity whereas belt accelerations on a treadmill have high-clinical feasibility for perturbation-based balance training (PBT). This study aimed to (i) compare adaptations to repeated overground trips with repeated treadmill belt accelerations in older adults and (ii) determine if adaptations to repeated treadmill belt accelerations can transfer to an actual trip on the walkway.

Method: Thirty-eight healthy community-dwelling older adults underwent one session each of walkway and treadmill PBT in a randomised crossover design on a single day. For both conditions, 11 trips were induced to either leg in pseudo-random locations interspersed with 20 normal walking trials. Dynamic balance (e.g., margin of stability) and gait (e.g., step length) parameters from 3D motion capture were used to examine adaptations in the walkway and treadmill PBT and transfer of adaptation from treadmill PBT to a walkway trip.

Results: No changes were observed in normal (no-trip) gait parameters in both training conditions, except for a small (0.9 cm) increase in minimum toe elevation during walkway walks (P < 0.01). An increase in the margin of stability and recovery step length was observed during walkway PBT (P < 0.05). During treadmill PBT, an increased MoS, step length and decreased trunk sway range were observed (P < 0.05). These adaptations to treadmill PBT did not transfer to a walkway trip.

Conclusions: This study demonstrated that older adults could learn to improve dynamic stability by repeated exposure to walkway trips as well as treadmill belt accelerations. However, the adaptations to treadmill belt accelerations did not transfer to an actual trip. To enhance the utility of treadmill PBT for overground trip recovery performance, further development of treadmill PBT protocols is recommended to improve ecological authenticity.