bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radical Democratic Inclusion: Why We Should Lower the Voting Age to 12
Authors: O'Neill Martin 
Published: April 2022

AbstractDemocratic societies such as the United Kingdom have come to fail their young citizens, often sacrificing their interests in a political process that gives much greater weight to the preferences and interests of older citizens. Against this background of intergenerational injustice, this article presents the case for a shift in the political system in the direction of radical democratic inclusion of younger citizens, through reducing the voting age to 12. This change in the voting age can be justified directly, with reference to the status, interests, and capacities of younger citizens, and it can also be justified as a remedy to existing forms of intergenerational injustice. This change in the voting age would require a parallel transformation in the role of secondary schools as part of the ‘critical infrastructure' of a democratic society, which would be part of a broader shift towards a more genuinely democratic political culture. The proposal is defended against less radical alternatives (such as votes at 16) and more radical alternatives (such as votes for younger children). The article concludes with some reflections on democracy and intergenerational justice in light of the Covid pandemic and the climate emergency.
Hyperglycemia in pregnancy and developmental outcomes in children at 18–60 months of age: the PANDORA Wave 1 study
Authors: Titmuss Angela , D’Aprano Anita , Barzi Federica , Brown Alex D.H. , Wood Anna , Connors Christine , Boyle Jacqueline A. , Moore Elizabeth , OʼDea Kerin , Oats Jeremy , McIntyre H. David , Zimmet Paul , Shaw Jonathan E. , Craig Maria E. , Maple-Brown Louise J. 
Published: April 2022

AbstractThis study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.
Twins in Guinea-Bissau have a ‘thin-fat’ body composition compared to singletons
Authors: Wagh Rucha , Bjerregaard-Andersen Morten , Bandyopadhyay Souvik , Yajnik Pranav , Prasad Rashmi B. , Otiv Suhas , Byberg Stine , Hennild Ditte Egegaard , Gomes Gabriel Marciano , Christensen Kaare , Sodemann Morten , Jensen Dorte Møller , Yajnik Chittaranjan S. 
Published: April 2022

AbstractThe ‘thrifty phenotype’ hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data were available on 7–34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, −0.21, p = 0.055), weight (WAZ −0.73, p = 0.024) and BMI (BAZ −0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.
Normierung und testtheoretische Überprüfung der deutschen Adaptation der Kurzform der Self-Control Scale (SCS-K-D)
Authors: Singh Ranjit Konrad 
Published: April 2022

Zusammenfassung. Gegenstand dieses Artikels ist die deutsche Adaptation der Kurzform der Self-Control Scale (SCS-K-D; übersetzt von Bertrams und Dickhäuser). Es werden 3 Ziele verfolgt: (1) Die Dimensionalität der Skala formal zu prüfen, (2) die Skala auf Messinvarianz bezüglich Geschlecht, Bildung und Alter zu prüfen und (3) basierend auf einer Zufallsstichprobe der erwachsenen deutschen Bevölkerung ( N = 4 038) Normwerte abzuleiten. Die theoretisch erwartete eindimensionale Struktur konnte empirisch nicht bestätigt werden. Wird der Einfluss invertierter Items mit einem Methodenfaktor kontrolliert, verbessert sich die Modellgüte. Für eine angemessene Modellgüte musste die 13-Item Skala jedoch zusätzlich durch Itemausschluss auf eine 8-Item Skala reduziert werden. Diese 8-Item Variante erreichte auch in einer zweiten, unabhängigen Stichprobe ( N = 1 818) eine akzeptable Güte. Die Überprüfung der durch Messinvarianz erfolgte 8-Item Variante mit Methodenfaktor ergab skalare Messinvarianz für Geschlecht, konfigurale Messinvarianz für Bildung und deutliche Messinvarianzprobleme über Altersgruppen hinweg. Normwerte für die erwachsene, deutsche Bevölkerung werden sowohl für die 13-Item und die 8-Item Variante zur Verfügung gestellt und zudem differenziert nach Bildungsniveau und Alter dargeboten.
Sensitivity of Global Ocean Deoxygenation to Vertical and Isopycnal Mixing in an Ocean Biogeochemistry Model
Authors: Ito T. , Takano Y. , Deutsch C. , Long M. C. 
Published: April 2022

AbstractLarge‐scale loss of oxygen under global warming is termed “ocean deoxygenation” and is caused by the imbalance between physical supply and biological consumption of oxygen in the ocean interior. Significant progress has been made in the theoretical understanding of ocean deoxygenation; however, many questions remain unresolved. The oxygen change in the tropical thermocline is poorly understood, with diverging projections among different models. Physical oxygen supply is controlled by a suite of processes that transport oxygen‐rich surface waters into the interior ocean, which is expected to weaken due to increasing stratification under global warming. Using a numerical model and a series of sensitivity experiments, the role of ocean mixing is examined in terms of effects on the mean state and the response to a transient warming. Both vertical and horizontal (isopycnal) mixing coefficients are systematically varied over a wide range, and the resulting oxygen distributions in equilibrated and transient simulations are examined. The spatial patterns of oxygen loss are sensitive to both vertical and isopycnal mixing, and the sign of tropical oxygen trend under climate warming can reverse depending on the choice of mixing parameters. An elevated level of isopycnal mixing disrupts the vertical advective‐diffusive balance of the tropical thermocline, increasing the mean state oxygen as well as the magnitude of the transient oxygen decline. These results provide first‐order explanations for the diverging behaviors of simulated tropical oxygen with respect to ocean mixing parameters.
Internet addiction and its association with quality of life in patients with major depressive disorder: a network perspective
Authors: Bai Wei , Cai Hong , Wu Siqi , Zhang Ling , Feng Ke-Xin , Li Yu-Chen , Liu Huan-Zhong , Du Xiangdong , Zeng Zhen-Tao , Lu Chang-Mou , Mi Wen-Fang , Zhang Lan , Ding Yan-Hong , Yang Juan-Juan , Jackson Todd , Cheung Teris , An Feng-Rong , Xiang Yu-Tao 
Published: April 2022

AbstractDepressive disorders and internet addiction (IA) are often comorbid. The aims of this study were to examine the network structure of IA in patients with major depressive disorders (MDD) and explore the association between IA and quality of life (QoL) in this population. This was a multicenter, cross-sectional survey. IA and QoL were assessed with the Internet Addiction Test (IAT) and the World Health Organization Quality of Life-brief version, respectively. Node expected influence (EI) was used to identify central symptoms in the network model, while the flow network of QoL was generated to examine its association with IA. A total of 1,657 patients with MDD was included. “Preoccupation with the Internet,” “Job performance or productivity suffer because of the Internet,” and “Neglect chores to spend more time online” were central symptoms. The symptom “Form new relationships with online users” had the strongest direct positive relation with QoL, while “Spend more time online over going out with others” and “Job performance or productivity suffer because of the Internet” had the strongest direct negative relations with QoL. Neglecting work caused by IA correlated with QoL, while making friends online appropriately was related to better QoL among MDD patients. Appropriate interventions targeting the central symptoms may potentially prevent or reduce the risk of IA in MDD patients.
Sleep in Alzheimer’s disease: a systematic review and meta-analysis of polysomnographic findings
Authors: Zhang Ye , Ren Rong , Yang Linghui , Zhang Haipeng , Shi Yuan , Okhravi Hamid R. , Vitiello Michael V. , Sanford Larry D. , Tang Xiangdong 
Published: April 2022

AbstractPolysomnography (PSG) studies of sleep changes in Alzheimer’s disease (AD) have reported but not fully established the relationship between sleep disturbances and AD. To better detail this relationship, we conducted a systematic review and meta-analysis of reported PSG differences between AD patients and healthy controls. An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO inception to Mar 2021. Twenty-eight studies were identified for systematic review, 24 of which were used for meta-analysis. Meta-analyses revealed significant reductions in total sleep time, sleep efficiency, and percentage of slow-wave sleep (SWS) and rapid eye movement (REM) sleep, and increases in sleep latency, wake time after sleep onset, number of awakenings, and REM latency in AD compared to controls. Importantly, both decreased SWS and REM were significantly associated with the severity of cognitive impairment in AD patients. Alterations in electroencephalogram (EEG) frequency components and sleep spindles were also observed in AD, although the supporting evidence for these changes was limited. Sleep in AD is compromised with increased measures of wake and decreased TST, SWS, and REM sleep relative to controls. AD-related reductions in SWS and REM sleep correlate with the degree of cognitive impairment. Alterations in sleep EEG frequency components such as sleep spindles may be possible biomarkers with relevance for diagnosing AD although their sensitivity and specificity remain to be clearly delineated. AD-related sleep changes are potential targets for early therapeutic intervention aimed at improving sleep and slowing cognitive decline.
Desmosterol and 7-dehydrocholesterol concentrations in post mortem brains of depressed people: The role of trazodone
Authors: Cenik Basar , Palka Jayme M. , Thompson Bonne M. , McDonald Jeffrey G. , Tamminga Carol A. , Cenik Can , Brown E. Sherwood 
Published: April 2022

AbstractMajor depressive disorder (MDD) is a common, disabling, and heterogeneous condition that responds unpredictably to current treatments. We previously showed an association between depressive symptoms and plasma concentrations of two cholesterol precursors, desmosterol and 7-dehydrocholesterol (7DHC). Here, we measured total cholesterol and sterol concentrations with mass spectrometry in postmortem brain samples from depressed and control subjects. Mean (±SEM) desmosterol concentration was 8.9 ± 0.97 ng/mg in the depressed versus 10.7 ± 0.72 ng/mg in the control group. The mean of the posterior probability distribution for the difference in desmosterol concentration between the two groups was 2.36 (95% highest density interval [HDI] 0.59–4.17). Mean 7DHC concentrations, 12.5 ± 4.1 ng/mg in the depressed versus 5.4 ± 0.74 ng/mg in the control group, were unlikely to be different (95% HDI, [−1.37–0.34]). We found that presence of trazodone in the peri-mortem toxicology screen accounted for the observed difference in desmosterol concentrations. We also observed extremely high 7DHC levels in all 4 subjects who had taken trazodone. Trazodone has been recently found to inhibit 7-dehydrocholesterol reductase and alter sterol concentrations in rodents, cell culture, human fibroblasts, and blood. In this study, we demonstrate for the first time that trazodone alters human brain sterol composition. Given congenital deficiency of 7-dehydrocholesterol reductase results in Smith-Lemli-Opitz syndrome, our findings support the hypothesis that this commonly used medication may have previously unappreciated risks.
Adipose tissue aging: mechanisms and therapeutic implications
Authors: Ou Min-Yi , Zhang Hao , Tan Poh-Ching , Zhou Shuang-Bai , Li Qing-Feng 
Published: April 2022

AbstractAdipose tissue, which is the crucial energy reservoir and endocrine organ for the maintenance of systemic glucose, lipid, and energy homeostasis, undergoes significant changes during aging. These changes cause physiological declines and age-related disease in the elderly population. Here, we review the age-related changes in adipose tissue at multiple levels and highlight the underlying mechanisms regulating the aging process. We also discuss the pathogenic pathways of age-related fat dysfunctions and their systemic negative consequences, such as dyslipidemia, chronic general inflammation, insulin resistance, and type 2 diabetes (T2D). Age-related changes in adipose tissue involve redistribution of deposits and composition, in parallel with the functional decline of adipocyte progenitors and accumulation of senescent cells. Multiple pathogenic pathways induce defective adipogenesis, inflammation, aberrant adipocytokine production, and insulin resistance, leading to adipose tissue dysfunction. Changes in gene expression and extracellular signaling molecules regulate the aging process of adipose tissue through various pathways. In addition, adipose tissue aging impacts other organs that are infiltrated by lipids, which leads to systemic inflammation, metabolic system disruption, and aging process acceleration. Moreover, studies have indicated that adipose aging is an early onset event in aging and a potential target to extend lifespan. Together, we suggest that adipose tissue plays a key role in the aging process and is a therapeutic target for the treatment of age-related disease, which deserves further study to advance relevant knowledge.
Tumor suppressive role of microRNA-4731-5p in breast cancer through reduction of PAICS-induced FAK phosphorylation
Authors: Lang Lei , Tao Jing , Yang Chaomei , Li Wei 
Published: April 2022

AbstractA wide array of microRNAs (miRNAs) is differentially expressed in breast tumors and also functions as tumor suppressors. Herein, the current study sought to unravel the function of miR-4731-5p in breast cancer progression. First, breast cancer-related miRNA and mRNA microarray data sets were retrieved for differential analyses. Subsequently, the expression patterns of miR-4731-5p, PAICS, and FAK in breast cancer tissues and cells were determined, in addition to analyses of their roles in glycometabolism, migration, invasion, epithelial–mesenchymal transition (EMT) analyzed through functional assays. Next, the targeting relation between miR-4731-5p and PAICS was validated. Xenograft tumors in nude mice were further established to reproduce and verify the in vitro findings. miR-4731-5p was poorly expressed and PAICS was highly expressed in breast cancer tissues and cells. PAICS was confirmed as a target of miR-4731-5p. Moreover, miR-4731-5p exerted an inhibitory effect on glycolysis, EMT, migration, and invasion in breast cancer cells via regulation of PAICS-dependent phosphorylation of FAK. In vivo assay further validated the significance of the miR-4731-5p/PAICS/FAK axis in vivo tumorigenesis and lung metastasis in breast cancer. Collectively, our findings indicated that miR-4731-5p inhibited breast cancer cell glycolysis and EMT through the reduction of PAICS-induced phosphorylation of FAK.
FMNL2 suppresses cell migration and invasion of breast cancer: a reduction of cytoplasmic p27 via RhoA/LIMK/Cofilin pathway
Authors: Jiao Xinyan , Wang Bo , Yang Lu , Zhao Qingbin , Zhang Miao , Liu Xiaoxu , Zhou Can , Wang Ruiqi , Chen He , Wang Jichang , Ren Yu , Liu Peijun 
Published: April 2022

AbstractFormin-like protein 2 (FMNL2) belongs to a highly conserved family of cytoskeletal remodeling proteins that have been reported to be implicated in various actin-dependent physiological and cancer-associated processes. In this study, we mainly investigated the effects of FMNL2 on breast cancer cell migration and invasion, and the underlying mechanisms involved. We found that FMNL2 reduced cell migration and invasion of breast cancer in vitro and in vivo. Further, FMNL2 disrupted actin cytoskeleton rearrangement and hampered the RhoA/LIMK/Cofilin pathway in breast cancer cells. Critically, both Rho inhibitor ZOL and LIMK inhibitor BMS3 significantly abrogated these migration-promoting effects in FMNL2-silencing MDA-MB-231 and BT549 cells. RhoA/LIMK/Cofilin pathway was involved in FMNL2 silencing-induced actin cytoskeleton rearrangement in MDA-MB-231 and BT549 cells. More importantly, cytoplasmic p27 promoted FMNL2-mediated cell migration and invasion through RhoA/LIMK/Cofilin pathway in MCF7 and MDA-MB-231 cells. In addition, the expression and prognosis of FMNL2 were associated with ER in breast cancer. Furthermore, ERα overexpression reduced the protein levels of FMNL2 in breast cancer cells, which were reversed by MG132. In conclusion, FMNL2 suppressed cell migration and invasion of breast cancer by inhibiting RhoA/LIMK/Cofilin pathway through a reduction of cytoplasmic p27. This finding implies that the interference of FMNL2-mediated RhoA/LIMK/Cofilin pathway involving the cytoplasmic p27 may be a promising strategy for ameliorating breast cancer metastasis and prognosis.
GDF-15 in tumor-derived exosomes promotes muscle atrophy via Bcl-2/caspase-3 pathway
Authors: Zhang Wanli , Sun Weikuan , Gu Xiaofan , Miao Chunxiao , Feng Lixing , Shen Qiang , Liu Xuan , Zhang Xiongwen 
Published: April 2022

AbstractTumor-derived exosomes are emerging mediators of cancer cachexia, a kind of multifactorial syndrome characterized by serious loss of skeletal muscle mass and function. Our previous study had showed that microRNAs in exosomes of C26 colon tumor cells were involved in induction of muscle atrophy. Here, we focus on studying proteins in tumor-derived exosomes which might also contribute to the development of cancer cachexia. Results of comparing the protein profiles of cachexic C26 exosomes and non-cachexic MC38 exosomes suggested that growth differentiation factor 15 (GDF-15) was rich in C26 exosomes. Western blotting analysis confirmed the higher levels of GDF-15 in C26 cells and C26 exosomes, compared with that of MC38 cells. Results of animal study also showed that GDF-15 was rich in tumor tissues, serum exosomes, and gastrocnemius (GA) muscle tissues of C26 tumor-bearing mice. GDF-15 protein could directly induce muscle atrophy of cultured C2C12 myotubes via regulating Bcl-2/caspase-3 pathways. What’s more, overexpression of GDF-15 in MC38 cells could increase the potency of MC38 conditioned medium or exosomes in inducing muscle atrophy. Knockdown of GDF-15 in C26 cells decreased the potency of C26 conditioned medium or exosomes in inducing muscle atrophy. These results suggested that GDF-15 in tumor-derived exosomes could contribute to induction of muscle atrophy and also supported the possibility of targeting GDF-15 in treatment of cancer cachexia.
Targeting lncRNAs in programmed cell death as a therapeutic strategy for non-small cell lung cancer
Authors: Luo Yanqin , Li Jingyang , Yu Peng , Sun Jiayi , Hu Yingfan , Meng Xianli , Xiang Li 
Published: April 2022

AbstractLung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the most common histological type. Owing to the limited therapeutic efficacy and side effects of currently available therapies for NSCLC, it is necessary to identify novel therapeutic targets for NSCLC. Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs with a transcript length of more than 200 nucleotides, which play a vital role in the tumorigenesis and progression of multiple cancers, including NSCLC. Induction of programmed cell death (PCD) is the main mechanism leading to tumour cell death in most cancer treatments. Recent studies have demonstrated that lncRNAs are closely correlated with PCD including apoptosis, pyroptosis, autophagy and ferroptosis, which can regulate PCD and relevant death pathways to affect NSCLC progression and the efficacy of clinical therapy. Therefore, in this review, we focused on the function of lncRNAs in PCD of NSCLC and summarized the therapeutic role of targeting lncRNAs in PCD for NSCLC treatment, aiming to provide new sights into the underlying pathogenic mechanisms and propose a potential new strategy for NSCLC therapy so as to improve therapeutic outcomes with the ultimate goal to benefit the patients.