bluuebunny/crossref_metadata_2025_split 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 &lt; 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.
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

ObjectiveTo identify optimal machine-learning methods for the radiomics-based differentiation of gliosarcoma (GSM) from glioblastoma (GBM).Materials and MethodsThis 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.ResultsBased 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 &lt; 0.05). Furthermore, the sensitivity, specificity, and accuracy of the best radiomics model were superior to those obtained by the neuroradiologists.ConclusionOur 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.
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

BackgroundThe 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.MethodsGene 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.Results656 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.ConclusionsASF1B 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&lt; 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.
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.
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.
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.