bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Trimethylamine N-Oxide and Its Precursor With Cerebral Small Vessel Imaging Markers
Authors: Chen Yiyi , Xu Jie , Pan Yuesong , Yan Hongyi , Jing Jing , Yang Yingying , Wang Xing , Wan Huijuan , Gao Ying , Han Shangrong , Zhong Xi , Liu Chenhui , Pi Jingtao , Li Zhengyang , Luo Biyang , Wang Guangyao , Zhao Yilong , Wang Nan , Lin Jinxi , Meng Xia , Zhao Xingquan , Liu Liping , Li Wei , Jiang Yong , Li Zixiao , Zhang Xinmiao , Yang Xiaomeng , Ji Ruijun , Wang Chunjuan , Li Hao , Wang Penglian , Zheng Huaguang , Ji Weizhong , Cai Xueli , Wu Songdi , Han Xinsheng , Wang Yongjun , Wang Yilong
Published: April 2021

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds.

Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions.

Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0–2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1–2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9–1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease.

Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden.
Cerebral Metabolism Related to Cognitive Impairments in Multiple System Atrophy
Authors: Shen Cong , Chen Li , Ge Jing-Jie , Lu Jia-Ying , Chen Qi-Si , He Shu-Jin , Li Xin-Yi , Zhao Jue , Sun Yi-Min , Wu Ping , Wu Jian-Jun , Liu Feng-Tao , Wang Jian
Published: April 2021

Objective: We aimed to characterize the cognitive profiles in multiple system atrophy (MSA) and explore the cerebral metabolism related to the cognitive decline in MSA using 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET).

Methods: In this study, 105 MSA patients were included for cognitive assessment and 84 of them were enrolled for 18F-FDG PET analysis. The comprehensive neuropsychological tests covered five main domains including execution, attention, memory, language, and visuospatial function. The cognitive statuses were classified to MSA with normal cognition (MSA-NC) and MSA with cognitive impairment (MSA-CI), including dementia (MSA-D), and mild cognitive impairment (MSA-MCI). With 18F-FDG PET imaging, the cerebral metabolism differences among different cognitive statuses were analyzed using statistical parametric mapping and post-hoc analysis.

Results: Among 84 MSA patients, 52 patients were found with MSA-CI, including 36 patients as MSA-MCI and 16 patients as MSA-D. In detail, the cognitive impairments were observed in all the five domains, primarily in attention, executive function and memory. In 18F-FDG PET imaging, MSA-D and MSA-MCI patients exhibited hypometabolism in left middle and superior frontal lobe compared with MSA-NC (p < 0.001). The normalized regional cerebral metabolic rate of glucose (rCMRglc) in left middle frontal lobe showed relative accuracy in discriminating MSA-CI and MSA-NC [areas under the curve (AUC) = 0.750; 95%CI = 0.6391–0.8609].

Conclusions: Cognitive impairments were not rare in MSA, and the hypometabolism in frontal lobe may contribute to such impairments.
Predictors and Correlates of Depression in Retired Elite Level Rugby League Players
Authors: Iverson Grant L. , Van Patten Ryan , Terry Douglas P. , Levi Christopher R. , Gardner Andrew J.
Published: April 2021

Background: There is considerable interest in determining whether later-in-life depression is associated with lifetime history of concussions or the duration of a career in professional contact and collision sports. Rugby league is a high-intensity collision sport involving a large number of tackles per game and a high rate of concussions. We examined predictors and correlates of depression in retired elite level rugby league players in Australia.

Methods: Retired elite level rugby league players (N = 141, age: M = 52.6, SD = 13.8; Range = 30–89 years) completed the Depression, Anxiety, and Stress Scale (DASS), Brief Pain Inventory, Connor-Davidson Resilience Scale (CD-RISC), and Epworth Sleepiness Scale; they also reported on lifetime history of concussions. The DASS depression score was regressed on age, total number of self-reported concussions, years played professionally, CD-RISC score, BPI pain interference score, and ESS score.

Results: The retired players reported a median of 15 total lifetime concussions [interquartile range (IQR) = 6–30], and a median of 8 years playing professional sports (IQR = 3.5–11). The proportion of the sample endorsing at least mild current depression was 29%. The DASS depression score was positively correlated with the DASS anxiety (r = 0.54) and DASS stress scores (r = 0.58). The CD-RISC score was negatively correlated with the depression score (r = −0.53). Depression scores were not significantly correlated with pain severity (r = 0.14), and were weakly correlated with life interference due to pain (r = 0.20) and years playing professional sports (r = −0.17). Depression scores were not significantly correlated with lifetime history of concussions (r = 0.14). A multiple regression model, with age, total number of self-reported concussions, years played professionally, the CD-RISC, Brief Pain Inventory-pain interference score, and Epworth Sleepiness Scale score as predictors was significant, with 35% of the variance in DASS depression accounted for. The two significant independent predictors of depression were lower resilience and greater life interference due to pain.

Conclusions: This is the first large study of depression in retired rugby league players. Depression in these retired players was not meaningfully associated with lifetime history of concussions or number of years playing elite level collision sport. Depression was associated with current anxiety, stress, resilience, and life interference due to chronic pain.
Effects of Age on Cortical Tracking of Word-Level Features of Continuous Competing Speech
Authors: Mesik Juraj , Ray Lucia , Wojtczak Magdalena
Published: April 2021

Speech-in-noise comprehension difficulties are common among the elderly population, yet traditional objective measures of speech perception are largely insensitive to this deficit, particularly in the absence of clinical hearing loss. In recent years, a growing body of research in young normal-hearing adults has demonstrated that high-level features related to speech semantics and lexical predictability elicit strong centro-parietal negativity in the EEG signal around 400 ms following the word onset. Here we investigate effects of age on cortical tracking of these word-level features within a two-talker speech mixture, and their relationship with self-reported difficulties with speech-in-noise understanding. While undergoing EEG recordings, younger and older adult participants listened to a continuous narrative story in the presence of a distractor story. We then utilized forward encoding models to estimate cortical tracking of four speech features: (1) word onsets, (2) “semantic” dissimilarity of each word relative to the preceding context, (3) lexical surprisal for each word, and (4) overall word audibility. Our results revealed robust tracking of all features for attended speech, with surprisal and word audibility showing significantly stronger contributions to neural activity than dissimilarity. Additionally, older adults exhibited significantly stronger tracking of word-level features than younger adults, especially over frontal electrode sites, potentially reflecting increased listening effort. Finally, neuro-behavioral analyses revealed trends of a negative relationship between subjective speech-in-noise perception difficulties and the model goodness-of-fit for attended speech, as well as a positive relationship between task performance and the goodness-of-fit, indicating behavioral relevance of these measures. Together, our results demonstrate the utility of modeling cortical responses to multi-talker speech using complex, word-level features and the potential for their use to study changes in speech processing due to aging and hearing loss.
Constructing Dynamic Brain Functional Networks via Hyper-Graph Manifold Regularization for Mild Cognitive Impairment Classification
Authors: Ji Yixin , Zhang Yutao , Shi Haifeng , Jiao Zhuqing , Wang Shui-Hua , Wang Chuang
Published: April 2021

Brain functional networks (BFNs) constructed via manifold regularization (MR) have emerged as a powerful tool in finding new biomarkers for brain disease diagnosis. However, they only describe the pair-wise relationship between two brain regions, and cannot describe the functional interaction between multiple brain regions, or the high-order relationship, well. To solve this issue, we propose a method to construct dynamic BFNs (DBFNs) via hyper-graph MR (HMR) and employ it to classify mild cognitive impairment (MCI) subjects. First, we construct DBFNs via Pearson’s correlation (PC) method and remodel the PC method as an optimization model. Then, we use k-nearest neighbor (KNN) algorithm to construct the hyper-graph and obtain the hyper-graph manifold regularizer based on the hyper-graph. We introduce the hyper-graph manifold regularizer and the L1-norm regularizer into the PC-based optimization model to optimize DBFNs and obtain the final sparse DBFNs (SDBFNs). Finally, we conduct classification experiments to classify MCI subjects from normal subjects to verify the effectiveness of our method. Experimental results show that the proposed method achieves better classification performance compared with other state-of-the-art methods, and the classification accuracy (ACC), the sensitivity (SEN), the specificity (SPE), and the area under the curve (AUC) reach 82.4946 ± 0.2827%, 77.2473 ± 0.5747%, 87.7419 ± 0.2286%, and 0.9021 ± 0.0007, respectively. This method expands the MR method and DBFNs with more biological significance. It can effectively improve the classification performance of DBFNs for MCI, and has certain reference value for the research and auxiliary diagnosis of Alzheimer’s disease (AD).
Ferroptosis: Biochemistry and Biology in Cancers
Authors: Shi Zhiyuan , Zhang Lei , Zheng Jianzhong , Sun Huimin , Shao Chen
Published: April 2021

The challenge of eradicating cancer is that cancer cells possess diverse mechanisms to protect themselves from clinical strategies. Recently, ferroptosis has been shown to exhibit appreciable anti-tumor activity that could be harnessed for cancer therapy in the future. Ferroptosis is an iron-dependent form of regulated cell death that is characterized by the oxidization of polyunsaturated fatty acids (PUFAs) and accumulation of lipid peroxides. Ferroptosis has been closely correlated with numerous biological processes, such as amino acid metabolism, glutathione metabolism, iron metabolism, and lipid metabolism, as well as key regulators including GPX4, FSP1, NRF2, and p53. Although ferroptosis could be involved in killing various cancer cells, multiple aspects of this phenomenon remain unresolved. In this review, we summarize the biochemistry and biology of ferroptosis in diverse cancers and discuss the potential mechanisms of ferroptosis, which might pave the way for guiding cancer therapeutics.
Personalized Image-Guided Therapies for Local Malignencies: Interdisciplinary Options for Interventional Radiology and Interventional Radiotherapy
Authors: Kovács Attila , Bischoff Peter , Haddad Hathal , Kovács György , Schaefer Andreas , Zhou Willi , Pinkawa Michael
Published: April 2021

Minimal-invasive interventions considerably extend the therapeutic spectrum in oncology and open new dimensions in terms of survival, tolerability and patient-friendliness. Through the influence of image-guided interventions, many interdisciplinary therapy concepts have significantly evolved, and this process is by far not yet over. The rapid progression of minimal-invasive technologies offers hope for new therapeutic concepts in the short, medium and long term. Image-guided hybrid-technologies complement and even replace in selected cases classic surgery. In this newly begun era of immune-oncology, interdisciplinary collaboration and the focus on individualized and patient-friendly therapies are crucial.
Capilliposide C from Lysimachia capillipes Restores Radiosensitivity in Ionizing Radiation-Resistant Lung Cancer Cells Through Regulation of ERRFI1/EGFR/STAT3 Signaling Pathway
Authors: Wu Kan , Chen Xueqin , Feng Jianguo , Zhang Shirong , Xu Yasi , Zhang Jingjing , Wu Qiong , You Mingliang , Xia Bing , Ma Shenglin
Published: April 2021

Aims

Radiation therapy is used as the primary treatment for lung cancer. Unfortunately, radiation resistance remains to be the major clinic problem for lung cancer patients. Lysimachia capillipes capilliposide C (LC-C), an extract from LC Hemsl, has demonstrated multiple anti-cancer effects in several types of cancer. Here, we investigated the potential therapeutic impacts of LC-C on radiosensitivity in lung cancer cells and their underlying mechanisms.

Methods

Non-small cell lung cancer cell lines were initially irradiated to generate ionizing radiation (IR)-resistant lung cancer cell lines. RNA-seq analysis was used to examine the whole-transcriptome alteration in IR-resistant lung cancer cells treated with or without LC-C, and the differentially expressed genes with most significance were verified by RT-qPCR. Colony formation assays were performed to determine the effect of LC-C and the target gene ErbB receptor feedback inhibitor 1 (ERRFI1) on radiosensitivity of IR-resistant lung cancer cells. In addition, effects of ERRFI1 on cell cycle distribution, DNA damage repair activity were assessed by flow cytometry and γ-H2AX immunofluorescence staining respectively. Western blotting was performed to identify the activation of related signaling pathways. Tumor xenograft experiments were conducted to observe the effect of LC-C and ERRFI1 on radiosensitivity of IR-resistant lung cancer cells in vivo.

Results

Compared with parental cells, IR-resistant lung cancer cells were more resistant to radiation. LC-C significantly enhanced the effect of radiation in IR-resistant lung cancer cells both in vitro and in vivo and validated ERRFI1 as a candidate downstream gene by RNA-seq. Forced expression of ERRFI1 alone could significantly increase the radiosensitivity of IR-resistant lung cancer cells, while silencing of ERRFI1 attenuated the radiosensitizing function of LC-C. Accordingly, LC-C and ERRFI1 effectively inhibited IR-induced DNA damage repair, and ERRFI1 significantly induced G2/M checkpoint arrest. Additional investigations revealed that down-regulation of EGFR/STAT3 pathway played an important role in radiosensitization between ERRFI1 and LC-C. Furthermore, the high expression level of ERRFI1 was associated with high overall survival rates in lung cancer patients.

Conclusions

Treatment of LC-C may serve as a promising therapeutic strategy to overcome the radiation resistance and ERRFI1 may be a potential therapeutic target in NSCLC.
An Integrative Pharmacology-Based Strategy to Uncover the Mechanism of Xiong-Pi-Fang in Treating Coronary Heart Disease with Depression
Authors: Zhang Lihong , Zhang Yu , Zhu Mingdan , Pei Limin , Deng Fangjun , Chen JinHong , Zhang Shaoqiang , Cong Zidong , Du Wuxun , Xiao Xuefeng
Published: April 2021

Objectives: This study aimed to explore the mechanism of Xiong-Pi-Fang (XPF) in the treatment of coronary heart disease (CHD) with depression by an integrative strategy combining serum pharmacochemistry, network pharmacology analysis, and experimental validation.

Methods: An ultrahigh performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method was constructed to identify compounds in rat serum after oral administration of XPF, and a component-target network was established using Cytoscape, between the targets of XPF ingredients and CHD with depression. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to deduce the mechanism of XPF in treating CHD with depression. Finally, in a chronic unpredictable mild stress (CUMS)-and isoproterenol (ISO)-induced rat model, TUNEL was used to detect the apoptosis index of the myocardium and hippocampus, ELISA and western blot were used to detect the predicted hub targets, namely AngII, 5-HT, cAMP, PKA, CREB, BDNF, Bcl-2, Bax, Cyt-c, and caspase-3.

Results: We identified 51 compounds in rat serum after oral administration of XPF, which mainly included phenolic acids, saponins, and flavonoids. Network pharmacology analysis revealed that XPF may regulate targets, such as ACE2, HTR1A, HTR2A, AKT1, PKIA, CREB1, BDNF, BCL2, BAX, CASP3, cAMP signaling pathway, and cell apoptosis process in the treatment of CHD with depression. ELISA analysis showed that XPF decreased Ang-II content in the circulation and central nervous system, inhibited 5-HT levels in peripheral circulation, and increased 5-HT content in the central nervous system and cAMP content in the myocardia and hippocampus. Meanwhile, western blot analysis indicated that XPF could upregulate the expression levels of PKA, CREB, and BDNF both in the myocardia and hippocampus. TUNEL staining indicated that the apoptosis index of myocardial and hippocampal cells increased in CUMS-and ISO-induced CHD in rats under depression, and XPF could increase the expression of Bcl-2, inhibit the expression of Bax, Cyt-c, and caspase-3, and rectify the injury of the hippocampus and myocardium, which exerted antidepressant and antimyocardial ischemia effects.

Conclusion: Our study proposed an integrated strategy, combining serum pharmacochemistry and network pharmacology to investigate the mechanisms of XPF in treating CHD with depression. The mechanism of XPF in treating CHD with depression may be related to the activation of the cAMP signaling pathway and the inhibition of the apoptosis.
Review of Natural Resources With Vasodilation: Traditional Medicinal Plants, Natural Products, and Their Mechanism and Clinical Efficacy
Authors: Tang Fei , Yan Hong-Ling , Wang Li-Xia , Xu Jin-Feng , Peng Cheng , Ao Hui , Tan Yu-Zhu
Published: April 2021

For decades, chronic diseases including cardiovascular and cerebrovascular diseases (CCVDs) have plagued the world. Meanwhile, we have noticed a close association between CCVDs and vascular lesions, such as hypertension. More focus has been placed on TMPs and natural products with vasodilation and hypotension. TMPs with vasodilatory and hypotensive activities are mainly from Compositae, Lamiaceae, and Orchidaceae (such as V. amygdalina Del., T. procuinbens L., M. glomerata Spreng., K. galanga L., etc.) whereas natural products eliciting vasorelaxant potentials were primarily from flavonoids, phenolic acids and alkaloids (such as apigenin, puerarin, curcumin, sinomenine, etc.). Furthermore, the data analysis showed that the vasodilatory function of TMPs was mainly concerned with the activation of eNOS, while the natural products were primarily correlated with the blockage of calcium channel. Thus, TMPs will be used as alternative drugs and nutritional supplements, while natural products will be considered as potential therapies for CCVDs in the future. This study provides comprehensive and valuable references for the prevention and treatment of hypertension and CCVDs and sheds light on the further studies in this regard. However, since most studies are in vitro and preclinical, there is a need for more in-depth researches and clinical trials to understand the potential of these substances.
MicroRNA-29c Acting on FOS Plays a Significant Role in Nonalcoholic Steatohepatitis Through the Interleukin-17 Signaling Pathway
Authors: Cai Chao , Chen Da-Zhi , Tu Han-Xiao , Chen Wen-Kai , Ge Li-Chao , Fu Tian-Tian , Tao Ying , Ye Sha-Sha , Li Ji , Lin Zhuo , Wang Xiao-Dong , Xu Lan-Man , Chen Yong-Ping
Published: April 2021

Nonalcoholic fatty liver disease is the most common hepatic disease in western countries and is even more ubiquitous in Asian countries. Our study determined that TH17/Treg cells were imbalanced in animal models. Based on our interest in the mechanism underlying TH17/Treg cell imbalance in nonalcoholic fatty liver mice, we conducted a joint bioinformatics analysis to further investigate this process. Common gene sequencing analysis was based on one trial from one sequencing platform, where gene expression analysis and enrichment analysis were the only analyses performed. We compared different sequencing results from different trials performed using different sequencing platforms, and we utilized the intersection of these analytical results to perform joint analysis. We used a bioinformatics analysis method to perform enrichment analysis and map interaction network analysis and predict potential microRNA sites. Animal experiments were also designed to validate the results of the data analysis based on quantitative polymerase chain reaction (qPCR) and western blotting. Our results revealed 8 coexisting differentially expressed genes (DEGs) and 7 hinge genes. The identified DEGs may influence nonalcoholic steatosis hepatitis through the interleukin-17 pathway. We found that microRNA-29c interacts with FOS and IGFBP1. Polymerase chain reaction analyses revealed both FOS and microRNA-29c expression in NASH mice, and western blot analyses indicated the same trend with regard to FOS protein levels. Based on these results, we suggest that microRNA-29c acts on FOS via the interleukin-17 signaling pathway to regulate TH17/Treg cells in NASH patients.
The Fate of Dietary Cholesterol in the Kissing Bug Rhodnius prolixus
Authors: Entringer Petter F. , Majerowicz David , Gondim Katia C.
Published: April 2021

Insects are unable to synthesize cholesterol and depend on the presence of sterols in the diet for cell membrane composition and hormone production. Thus, cholesterol absorption, transport, and metabolism are potential targets for vector and pest control strategies. Here, we investigate the dietary cholesterol absorption and tissue distribution in the kissing bug Rhodnius prolixus using radiolabeled cholesterol. Both the anterior and posterior midguts absorbed cholesterol from the ingested blood, although the anterior midgut absorbed more. We also observed esterified cholesterol labeling in the epithelium, indicating that midgut cells can metabolize and store cholesterol. Only a small amount of labeled cholesterol was found in the hemolymph, where it was mainly in the free form and associated with lipophorin (Lp). The fat body transiently accumulated cholesterol, showing a labeled cholesterol peak on the fifth day after the blood meal. The ovaries also incorporated cholesterol, but cumulatively. The insects did not absorb almost half of the ingested labeled cholesterol, and radioactivity was present in the feces. After injection of 3H-cholesterol-labeled Lp into females, a half-life of 5.5 ± 0.7 h in the hemolymph was determined. Both the fat body and ovaries incorporated Lp-associated cholesterol, which was inhibited at low temperature, indicating the participation of active cholesterol transport. These results help describe an unexplored part of R. prolixus lipid metabolism.
Point Mutations as Main Resistance Mechanism Together With P450-Based Metabolism Confer Broad Resistance to Different ALS-Inhibiting Herbicides in Glebionis coronaria From Tunisia
Authors: Hada Zeineb , Menchari Yosra , Rojano-Delgado Antonia M. , Torra Joel , Menéndez Julio , Palma-Bautista Candelario , de Prado Rafael , Souissi Thouraya
Published: April 2021

Resistance to acetolactate synthase (ALS) inhibiting herbicides has recently been reported in Glebionis coronaria from wheat fields in northern Tunisia, where the weed is widespread. However, potential resistance mechanisms conferring resistance in these populations are unknown. The aim of this research was to study target-site resistance (TSR) and non-target-site resistance (NTSR) mechanisms present in two putative resistant (R) populations. Dose–response experiments, ALS enzyme activity assays, ALS gene sequencing, absorption and translocation experiments with radiolabeled herbicides, and metabolism experiments were carried out for this purpose. Whole plant trials confirmed high resistance levels to tribenuron and cross-resistance to florasulam and imazamox. ALS enzyme activity further confirmed cross-resistance to these three herbicides and also to bispyribac, but not to flucarbazone. Sequence analysis revealed the presence of amino acid substitutions in positions 197, 376, and 574 of the target enzyme. Among the NTSR mechanisms investigated, absorption or translocation did not contribute to resistance, while evidences of the presence of enhanced metabolism were provided. A pretreatment with the cytochrome P450 monooxygenase (P450) inhibitor malathion partially synergized with imazamox in post-emergence but not with tribenuron in dose–response experiments. Additionally, an imazamox hydroxyl metabolite was detected in both R populations in metabolism experiments, which disappeared with the pretreatment with malathion. This study confirms the evolution of cross-resistance to ALS inhibiting herbicides in G. coronaria from Tunisia through TSR and NTSR mechanisms. The presence of enhanced metabolism involving P450 is threatening the chemical management of this weed in Tunisian wheat fields, since it might confer cross-resistance to other sites of action.
Proteomic Responses to Alkali Stress in Oats and the Alleviatory Effects of Exogenous Spermine Application
Authors: Bai Jianhui , Jin Ke , Qin Wei , Wang Yuqing , Yin Qiang
Published: April 2021

Alkali stress limits plant growth and yield more strongly than salt stress and can lead to the appearance of yellow leaves; however, the reasons remain unclear. In this study, we found that (1) the down-regulation of coproporphyrinogen III oxidase, protoporphyrinogen oxidase, and Pheophorbide a oxygenase in oats under alkali stress contributes to the appearance of yellow leaves (as assessed by proteome and western blot analyses). (2) Some oat proteins that are involved in the antioxidant system, root growth, and jasmonic acid (JA) and indole-3-acetic acid (IAA) synthesis are up-regulated in response to alkalinity and help increase alkali tolerance. (3) We added exogenous spermine to oat plants to improve their alkali tolerance, which resulted in higher chlorophyll contents and plant dry weights than in plants subjected to alkaline stress alone. This was due to up-regulation of chitinase and proteins related to chloroplast structure, root growth, and the antioxidant system. Spermine addition increased sucrose utilization efficiency, and promoted carbohydrate export from leaves to roots to increase energy storage in roots. Spermine addition also increased the IAA and JA contents required for root growth.
Dual Careers of Athletes During COVID-19 Lockdown
Authors: Izzicupo Pascal , Di Baldassarre Angela , Abelkalns Ilvis , Bisenieks Ugis , Sánchez-Pato Antonio , Cánovas-Alvarez Francisco José , Doupona Mojca , Figueiredo António J. , García-Roca Juan Alfonso , Ghinassi Barbara , Leiva-Arcas Alejandro , Meroño Lourdes , Paegle Anda , Radu Liliana-Elisabeta , Rus Cristian-Mihail , Rusu Oana-Mihaela , Sarmento Hugo , Stonis Janis , Vaquero-Cristóbal Raquel , Vaz Vasco , Capranica Laura
Published: April 2021

This study aimed to investigate the student-athletes' capability to face the academic, sport, and social challenges during the coronavirus disease 2019 (COVID-19) lockdown and to disclose novel aspects of dual careers. A 32-item online survey encompassing demographic characteristics, sport and university engagement, support and dual-career benefits, physical activity, sitting time, and the time deemed necessary to recover the previous level of performance was developed. Four hundred sixty-seven student-athletes (males: 57%, females: 43%) from 11 countries, competing in 49 different sports (individual: 63.4%, team: 36.6%) at regional (17.5%), national (43.3%), and international (39.2%) levels, and enrolled at high school (21.9%) and university (78.1%) levels completed the survey. During the lockdown, the respondents decreased the time dedicated to sport and academics, although they maintained an active lifestyle. Student-athletes from countries under severe contagion were more likely to train at home, dedicate to academics, and receive support from the coach but less likely receive support from their teachers. With respect to their team sport counterparts, athletes competing in individual sports trained more and were more likely to receive support from their coaches. International athletes showed the highest training time and support from their coaches and as student-athletes. High school students received more support from their coaches and teachers, whereas university students were more likely considering dual careers useful to cope with the COVID-19 pandemic. This study substantiates the relevant role of competitive sports participation in the maintenance of active lifestyles, with student-athletes considering home training and e-learning valuable resources during the lockdown. Furthermore, their sport and academic commitments helped student-athletes cope with the emergency of the COVID-19 pandemic.
Motivational Interviewing for Loved Ones in Early Psychosis: Development and Pilot Feasibility Trial of a Brief Psychoeducational Intervention for Caregivers
Authors: Kline Emily R. , Thibeau Heather , Sanders Aliyah S. , English Kelly , Davis Beshaun J. , Fenley Alicia R. , Keshavan Matcheri S.
Published: April 2021

Treatment delay and non-adherence in first episode psychosis is a pressing public health problem. Ambivalence regarding psychiatric intervention and labeling among young people with psychosis is a contributing factor. For these individuals, caregivers often facilitate the pathway to care and support ongoing engagement and adherence. Caregivers describe distress and burden associated with this role. This manuscript describes the development and pilot feasibility testing of a motivational interviewing-derived communication training for caregivers of individuals with untreated or under-treated early course psychosis. Individuals with lived experience were consulted in the intervention development process. The training consisted of four 60-min sessions teaching the philosophy and basic skills of motivational interviewing as well as two brief practice calls. Feasibility was assessed with regard to study enrollment, retention, and completion. Satisfaction was assessed through the Client Satisfaction Questionnaire and qualitative feedback. Thirty-one caregivers consented to this pilot feasibility trial and participated via telehealth over the course of 5 months. Intervention completion and reported satisfaction were high, with 94% of consented participants completing at least three training sessions and 84% reporting that they would “definitely” recommend the training to a friend in similar circumstances. There were no between-clinician differences in MILO session attendance (F[2] = 0.53, p = 0.596) or satisfaction total scores (F[2] = 1.03, p = 0.371). Brief motivational interviewing skills training appears to be a feasible and valued intervention for caregivers of individuals with poorly managed early course psychosis.

Clinical Trial Registration:ClinicalTrials.gov Identifier: NCT04010747
Evaluation of the Implementation of a 25-Year Outdoor School Ground Smoking Ban: A Qualitative Interview Study With Implications for Prevention Practise
Authors: Kvillemo Pia , Feltmann Kristin , Elgán Tobias H. , Gripenberg Johanna
Published: April 2021

Introduction: Tobacco use, often initiated in younger ages, is a serious health challenge worldwide. In Sweden, smoking has been prohibited on school grounds since 1994. Municipal environmental and health inspectors control the compliance of the ban. Nevertheless, the enforcement and maintenance of the ban are inadequate. The aim of the current study was to identify facilitators, barriers, and the potential for improved implementation of a 25-year outdoor school ground smoking ban in upper secondary schools.

Materials and Methods: A process evaluation was conducted using semi-structured interviews with principals in upper secondary schools, local environmental and health inspectors, and local politicians (n = 30) in Stockholm County, with purposive sampling for informant recruitment. A qualitative content analysis of the transcribed interviews was performed.

Results: Three main categories and 10 subcategories were generated from the interviews, revealing facilitators, barriers, and the potential for improvement of the implementation of the ban. A prominent facilitator of the ban was informed and engaged principals and inspectors. Prominent barriers were conflicting goals governing the schools, which reduce staffs' motivation to maintain the ban, unclear school ground boundaries, and lack of resources. Potential for improvement was found in a new tobacco act with an extended ban on smoking at school entrances, extended support for schools and staff to strictly enforce the ban, and a continued denormalisation of smoking in society.

Conclusion: To achieve effective implementation of outdoor school ground smoking bans in upper secondary schools, authorities need to address conflicts between different goals governing the schools and give necessary support to the staff to strictly enforce the ban. Policies on smoke-free working hours in the municipalities along with tobacco restrictive policies in the surrounding society may increase the possibility to maintain the smoking ban in upper secondary school grounds.
A Preliminary Embodiment Short Questionnaire
Authors: Eubanks James Coleman , Moore Alec G. , Fishwick Paul A. , McMahan Ryan P.
Published: April 2021

Consumer virtual reality (VR) technologies have made embodying a virtual avatar during an immersive experience more feasible. The sense of embodiment toward that virtual avatar can be characterized and measured along three factors: self-location, agency, and body ownership. Some measures of embodiment have been previously proposed, but most have not been validated or do not measure the three individual factors of embodiment. In this paper, we present the construction and validation of a preliminary version of a short questionnaire that not only addresses these factors of embodiment but can also be used as an in-VR questionnaire, which we call the pESQ. By using and validating the pESQ, we provide results indicating that foot tracking significantly improves self-location and agency, and that an avatar significantly improves body ownership.
The Unequal Distribution of Linguistic Capital in a Transnational Economic Order
Authors: Rössel Jörg , Schroedter Julia H.
Published: April 2021

Foreign language proficiency is an unequally distributed form of linguistic capital that is becoming increasingly important in contemporary societies: first, it enables persons to participate transnationally in educational activities and in labor markets beyond the national institutions of their home country. It is also crucial for integrating an increasing share of the population with a migration background into the labor market. Thus, this article focuses on the explanation of language proficiency. Its main aim is to enrich the discussion in this field by deriving hypotheses from the sociological theory of reproduction and the discourse on migrant integration. Variables are included which have not been tested in a broad fashion in previous empirical research. We use data on different groups of migrants and non-migrants in multilingual Switzerland, where we could study the determinants of the unequal distribution of language proficiency in three official languages and foreign language repertoire in general. Our main results show that the hypotheses derived from the two theoretical discussions are empirically supported overall and contribute substantially to the explanation of language proficiency. However, most of these variables indicate the importance of unequally distributed opportunities for learning languages, thus highlighting that language learning may be part of the general process of reproducing social inequality structures.
Blood Volume, Hemoglobin Mass, and Peak Oxygen Uptake in Older Adults: The Generation 100 Study
Authors: Lundgren Kari Margrethe , Aspvik Nils Petter , Langlo Knut Asbjørn Rise , Braaten Tonje , Wisløff Ulrik , Stensvold Dorthe , Karlsen Trine
Published: April 2021

Purpose: To investigate the association between blood volume, hemoglobin mass (Hbmass), and peak oxygen uptake (VO2peak) in healthy older adults.

Methods: Fifty fit or unfit participants from the prospective randomized Generation 100 Study (n = 1,566) were included (age- and sex-specific VO2peak above or below average values). Blood, plasma, and erythrocyte volume and Hbmass were tested using the carbon monoxide rebreathing method within 1 week after VO2peak testing.

Results: Mean age, BMI, Hbmass, blood volume, and VO2peak were 73.0 ± 2.1 years, 24.8 ± 3.3 kg·m2, 10.0 ± 1.7 g·kg−1, 76.4 ± 11.8 mL·kg−1, and 33.5 ± 8.4 mL·kg−1·min−1. VO2peak in fit and unfit participants and women and men were 38.6 ± 6.5 and 25.8 ± 3.8 mL·kg−1·min−1, 30.7 ± 7.6 mL·kg−1·min−1, and 35.5 ± 8.5 mL·kg−1·min−1, respectively. Women were shorter (Δ14 cm), leaner (Δ13 kg), and with less muscle mass (Δ9%) than men (P < 0.05). Relative erythrocyte volume and Hbmass were lower in women, and blood and erythrocyte volume and Hbmass were higher in the fit participants (P < 0.05). Hbmass and erythrocyte volume explained 40 and 37%, respectively, of the variability in VO2peak, with a limited effect of physical-activity adjustment (40 and 38%, respectively). Blood and plasma volume explained 15 and 25%, respectively, of VO2peak variability, and the association was strengthened adjusting for physical activity (25 and 31%, respectively), indicating a training-dependent adaptation in plasma but not erythrocyte volume (p ≤ 0.006).

Conclusions: Blood and plasma volumes were moderately associated with VO2peak in healthy older men and women, and the association was strengthened after adjustment for physical activity. Hbmass and erythrocyte volume were strongly associated with VO2peak but unrelated to physical activity.
Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis
Authors: Zhang Xi , Zhang Junjun , Liu Yang , Li Jie , Tan Juan , Song Zewen
Published: April 2021

Background: Bcl-2 associated athanogene2 (BAG2) is reported to act as an oncogene or a tumor-suppressor in tumors in a context-dependent way; however, its function in hepatocellular carcinoma (HCC) remains unclear.

Methods: Immunohistochemistry (IHC) staining, cell counting kit-8 (CCK-8) assay, apoptotic assay, cell invasion assay and a set of bioinformatics tools were integrated to analyze the role of BAG2 in hepatocellular carcinoma.

Results: BAG2 was significantly up-regulated in HCC. Prognostic analysis indicated that HCC patients with high expression of BAG2 had significantly shorter overall survival, progression free survival and disease specific survival. Besides, silencing BAG2 in HCC cells impaired cell proliferation, facilitated apoptosis and repressed invasion of the cells. Bioinformatics analysis showed that BAG2 might regulate ribosome biogenesis in HCC.

Conclusion: This study revealed that the up-regulated BAG2 in HCC was associated with a worse prognosis and might favor the progression of the disease.
Spatial Delimitation of Genetic Diversity of Native Maize and Its Relationship with Ethnic Groups in Mexico
Authors: Santillán-Fernández Alberto , Salinas-Moreno Yolanda , Valdez-Lazalde José , Bautista-Ortega Jaime , Pereira-Lorenzo Santiago
Published: April 2021

Mexico, as a center of origin of maize, presents a high diversity of maize races. With the objective of spatially demarcating regions with high concentration of intraspecific diversity in Mexico, as a fundamental measure for the in situ conservation of their agrobiodiversity, Geographic Information Systems (GIS) tools have been used to generate diversity and richness indexes for 64 maize races cultivated in Mexico, using indexes to demarcate relationships to environmental factors such as temperature, precipitation, and altitude; the presence of indigenous groups; and the type of maize used. These relations allowed defining seven environmental units spatially, with characteristic maize races in each of them, which constitute priority areas for in situ conservation. In addition, a close relationship was found between the diversity of maize races and of ethnic groups, from the center to the south of the country, associated with the differences in maize use in different ethnic groups. This geographical demarcation of races and uses of maize will favor food security through specific measures of in situ conservation, as well as an increase in added value of maize by-products based on specific maize races conserved by local ethnic groups.
Egg Quality Parameters, Production Performance and Immunity of Laying Hens Supplemented with Plant Extracts
Authors: Dilawar Muhammad Ammar , Mun Hong Seok , Rathnayake Dhanushka , Yang Eun Ju , Seo Ye Seul , Park Hyeoung Seog , Yang Chul Ju
Published: April 2021

This study examined the effects of Mentha arvensis (MA) and Geranium thunbergii (GT) extracts in drinking water on the production performance, egg quality, cholesterol content of egg yolk, proximate composition, and sensory qualities of egg and immunity parameters in laying hens. Ninety-six 28-week-old Hy-Line Brown layers were randomly divided into four dietary treatments for 16 weeks. The dietary treatments were (1) control, (2) T1 (0.01% 1 MA:1 GT), (3) T2 (0.05% 1 MA:1 GT), and (4) T3 (0.1% 1 MA:1 GT). Egg production increased significantly with increasing levels of MA and GT. The egg weight was increased in T2, and the feed intake was highest in T2 and T3 (p < 0.05). The Haugh unit and egg shape index were significantly better in T3 and the control than with other treatments (p < 0.05). The content of yolk cholesterol was significantly lower (p < 0.05) in T2 and T3. On the other hand, there were no significant differences in the egg proximate composition. A significant increase in the serum interleukin 6 (IL-6), tumor necrosis factor (TNFα) and immunoglobulins (IgG and IgA) concentration was observed in the birds fed plant extracts when compared to the control. On average, T2 and T3 showed significantly lower (p < 0.05) concentrations of NH3 gas from the feces as compared to the control. This study suggests that MA and GT supplementation could improve the laying performance, egg quality, and immunity, and decrease the egg yolk cholesterol content in a dose-dependent manner.
A Multi-Biomarker Approach in European Sea Bass Exposed to Dynamic Temperature Changes under Dietary Supplementation with Origanum vulgare Essential Oil
Authors: Dinardo Francesca Rita , Maggiolino Aristide , Casalino Elisabetta , Deflorio Michele , Centoducati Gerardo
Published: April 2021

A feeding trial for 150 days was carried out to evaluate the cross-effects between oregano essential oil (EO) dietary supplementation and dynamic temperature change in sea bass. Under exposure to rising temperature (13–25 °C), fish were fed with a control diet (CD) and two experimental diets supplemented with 100 (D100) and 200 ppm (D200) of EO. Feed inclusion of EO promoted the activity of antioxidant enzymes in sea bass exposed to increasing temperature. Consistently with the temperature rise, TBARS concentrations increased in CD and D200 groups, whereas were almost stable in D100. Trend of blood glucose in fish fed on CD was likely affected by glycogenolysis and gluconeogenesis. Similarly, the depletion of triglycerides and cholesterol in fish fed on CD likely supported the energy cost of gluconeogenesis. On the other hand, the reduction of glucose, triglycerides, and cholesterol in D100 and D200 was mainly attributable to the hypoglycemic and hypolipidemic effects of EO. The higher levels of serum protein observed in D100 and D200 groups were also associated to a reduced thermal stress compared to CD. EO dietary supplementation may be a promising strategy to alleviate the negative effects of temperature shift on sea bass physiological and oxidative state.
Refinement of Animal Model of Colorectal Carcinogenesis through the Definition of Novel Humane Endpoints
Authors: Silva-Reis Rita , Faustino-Rocha Ana I. , Gonçalves Mariana , Ribeiro Catarina Castro , Ferreira Tiago , Ribeiro-Silva Carla , Gonçalves Lio , Antunes Luís , Venâncio Carlos , Ferreira Rita , Gama Adelina , Oliveira Paula A.
Published: April 2021

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid (EDTA)–saline solutions and two induced groups (CRC1 and CRC2) injected with 1,2-dimethylhydrazine (DMH) for seven weeks. A score sheet with 14 biological parameters was used to assess animal welfare. Groups CRC1 and CTRL1 and groups CRC2 and CTRL2 were euthanized 11 and 17 weeks after the first DMH administration, respectively. Five animals from the induced groups died unexpectedly during the protocol (survival rates of 75.0% and 66.7% for groups CRC1 and CRC2, respectively). The final mean body weight (BW) was smaller in the CRC groups when compared with that in the CTRL groups. A uniformity of characteristics preceding the premature animals’ death was observed, namely an increase of 10% in mean BW, swollen abdomen, diarrhea, and priapism. The surface abdominal temperature of group CRC2 was significantly higher, when compared with that of group CTRL2. The parameters already described in other cancer models proved to be insufficient. For the CRC model, we considered assessing the abdominal temperature, priapism, and sudden increase in the BW.