bluuebunny/crossref_metadata_2025_split huggingface dataset:
Policosanol attenuates Pi‐induced calcification via AMPK‐mediated INSIGs expression in rat VSMCs
Authors: Kim Kyeong‐Min , Kim Chang‐Hyun , Cho Kyung‐Hyun , Jang Won‐Gu 
Published: June 2021

AbstractPolicosanol is a hypocholesterolemic derived from sugar cane and corn that downregulates blood cholesterol levels. It can further lower blood pressure and reduce liver inflammation. Policosanol can also affect vascular calcification, however, its molecular mechanisms are not well understood. This study investigated the effect of policosanol on vascular calcification and its molecular mechanism. Policosanol decreased the expression of inorganic phosphate (Pi)‐induced osteogenic genes such as distal‐less homeobox 5 (Dlx5) and runt‐related transcription factor 2 (Runx2). In addition, following policosanol treatment, adenosine monophosphate‐activated protein kinase (AMPK) phosphorylation increased in a time‐dependent manner. The constitutively active form of AMPK (CA‐AMPK) dramatically suppressed Pi‐induced Dlx5 and Runx2 protein levels. Inactivation of AMPK using compound C (Com. C; AMPK inhibitor) recovered policosanol‐suppressed Alizarin Red S staining levels. Insulin‐induced genes (INSIGs) were induced by CA‐AMPK, their overexpression suppressed Pi‐induced Dlx5 and Runx2 expression. Taken together, the results demonstrate that policosanol inhibits Pi‐induced vascular calcification by regulating AMPK‐induced INSIG expression in vascular smooth muscle cells.
More scientific, more ethical: The ADHD controversy and boundary‐work in Taiwan
Authors: Tseng Fan‐Tzu 
Published: June 2021

AbstractAttention‐deficit/hyperactivity disorder (ADHD) is one of the most controversial childhood psychiatric condition. With the globalisation of its diagnosis and treatment, Taiwan has followed other medically advanced countries in meeting the challenge of medicalising children's problematic behaviours and encountering the resistance discourses on ADHD. To contribute to the extant literature, this study employs the social worlds framework to decipher the relational dynamics amongst these competing discourses on ADHD, namely the mainstream psychiatry, the critiques of overdiagnosis and the antipsychiatric protest, and to suggest the links between these domestic advocacies and the relevant debates abroad. In addition, the concept of boundary‐work is used to analyse the strategies through which these collective actors pursue legitimacy for their respective claims. Based on the existing research of scientific and ethical boundary‐work, this study argues that when it comes to clinical practices fraught with uncertainties, these two seemingly distinct forms of boundary‐work may become mutually supportive in order to act as arbiters of disputes. Despite the disparity of power amongst these social worlds in this case study with seemingly predictable outcomes of the dispute, representing their heterogeneous narratives and the process of discursive struggle helps to destabilise the seemingly naturalised conceptualisation of biomedical ADHD.
‘Dark’ and ‘Clear’ Y in Medieval Welsh Orthography: Caligula versus Teilo
Authors: Sims‐Williams Patrick 
Published: June 2021

AbstractA famous exception to the ‘phonetic spelling system’ of Welsh is the use of <y> for both /ǝ/ and the retracted high vowel /ɨ(:)/. This double use of <y> was almost universally adopted by c. 1330, when a grammarian labelled /ǝ/ and /ɨ/ as ‘dark y’ and ‘clear y’ and illustrated them with polysyllables such as ystyr /ˈǝstɨr/ ‘meaning’, in which the value of <y> was predictable from the position of <y> in the word. At that time the three‐way system of for /i(:)/, ‘dark’ <y>, and ‘clear’ <y> was two centuries old, being first attested in Braint Teilo (‘The Privilege of St Teilo’), c. 1130. Yet the ‘Teilo’ system is rarely attested before c. 1300; instead all three phonemes might be represented by , as commonly before 1100, or by <y>; or <e> might be used for /ǝ/ and/or for /ɨ(:)/, as had sometimes occurred in Old Welsh as well. This article argues that one reason, apart from scribal conservatism, for the delay in adopting the ‘Teilo’ system was its failure to distinguish the value of <y> in proclitics such y /ǝ/ ‘the’ and y /ɨ/ ‘his/her’ and ‘to’. For this the ultimately abortive ‘Caligula’ system (c. 1250) had offered a solution.
FROM THE SANITARY CITY TO THE CIRCULAR CITY? Technopolitics of Wastewater Restructuring in Los Angeles, California
Authors: Meilinger Valentin , Monstadt Jochen 
Published: June 2021

AbstractThis article follows the flow of wastewater in Los Angeles, California, from upstream treatment plants to the Pacific Ocean, to explore struggles over reconfigurations of urban wastewater flows for new policy ambitions in recycling and reuse. We show how ambitious infrastructure visions of circular urban resource management have gained force since California's most recent drought (2011−17) but clash with incumbent gravity‐fed water and sewer systems, political economy and urban geographies. Engineers navigate these path dependencies through incremental technical improvements of existing infrastructures to increase wastewater recycling. These interventions largely reproduce given infrastructure configurations and urban geographies of water and wastewater while marginalizing other voices in struggles over water circularity and stymying critical debate about more progressive change. We argue that novel infrastructural practices are deeply political and normative and can be explained by four dimensions of the ‘technopolitics’ of wastewater restructuring in Los Angeles: materiality and inherited topologies of infrastructures; circularity discourses; entrenched knowledge cultures; and institutional orders of infrastructure management and public control mechanisms of infrastructure investments and tariffs. We conclude by discussing how these four dimensions of an emerging technopolitical regime of wastewater recycling expand concepts of power that explain urban metabolic change.
Using a situative perspective to gain a deeper understanding of how children’s strengths are related to social context
Authors: Bozic Nick , Lawthom Rebecca , Murray Janice , Oldfield Jeremy 
Published: June 2021

AbstractOver the last twenty‐five years, there has been an increase in the availability of published checklists and schedules which allow practitioners to identify the strengths of children and young people, including those with special educational needs. While helpful, these assessments are unable to tell us about the nature of contextual factors which support the expression of particular strengths. In this study, we took a situative perspective to explore how specific classroom practices facilitated strengths. A multiple case study design was used to analyse practices nominated by three children/young people with special educational needs. Qualitative analysis revealed how aspects of practice afforded the opportunity for each child to participate in ways which they equated with their strengths. This style of strength‐based assessment led to a more sustained examination of supportive practice features than would have been achieved through interview alone.
Narrative and metaphors in New Zealand’s efforts to eliminate COVID‐19
Authors: Kearns Robin 
Published: June 2021

AbstractThis commentary considers the ways in which spatialised metaphors were mobilised within a larger narrative in the quest to eliminate COVID‐19 in Aotearoa/New Zealand. In doing so, it examines the links between language and socio‐political discourse, focusing on tropes that invoke and engage with geographies of everyday life. The foundational contention is that, to a large extent, language constructs our lived reality. After reviewing scholarship linking language and disease, the commentary turns to a case study of New Zealand’s response to COVID‐19. The public health goal was to instil caution and protective practices in the population at large as a defence against transmission. The role of narrative and metaphor in daily press conferences from the Prime Minister and Director General of Health through March and April 2020 is examined by drawing on evidence from media reporting. Three key metaphors are considered: bubbles, levels, and the team, with each metaphor having spatialised implications in the popular imagination. The commentary considers perceptual and behavioural implications of this strategic use of metaphor. I speculate on the ways in which language has an agency such that, until the widespread availability of vaccine, an infectious disease can be restricted through mobilising the population.
The (ir)relevance of human resource management in independent work: Challenging assumptions
Authors: Cross David , Swart Juani 
Published: June 2021

AbstractWe challenge the assumption that independent workers are not relevant to or within the remit of HRM practice and theory. Traditionally, HR focusses on the management of employees within the boundaries of the organisation. Yet, this neglects the wider role that HR can and must have in the management of human work that the organisation needs yet exists beyond these boundaries. We argue for the ‘Human’ in HRM to include independent workers. We first contextualise them, highlight the reasons for neglect, and examine and provoke three key areas. We set out the taken for granted, problematise, and then show how they are relevant, look different, or could be. Through this, we provoke exactly what HR does, where it starts and finishes, and its role in a network or ecosystem rather than purely an organisation. We close by offering ways of making this happen for both theory and practice.
Clonal hematopoiesis associated with epigenetic aging and clinical outcomes
Authors: Nachun Daniel , Lu Ake T. , Bick Alexander G. , Natarajan Pradeep , Weinstock Joshua , Szeto Mindy D. , Kathiresan Sekar , Abecasis Goncalo , Taylor Kent D. , Guo Xiuqing , Tracy Russ , Durda Peter , Liu Yongmei , Johnson Craig , Rich Stephen S. , Van Den Berg David , Laurie Cecilia , Blackwell Tom , Papanicolaou George J. , Correa Adolfo , Raffield Laura M. , Johnson Andrew D. , Murabito Joanne , Manson JoAnn E. , Desai Pinkal , Kooperberg Charles , Assimes Themistocles L. , Levy Daniel , Rotter Jerome I. , Reiner Alex P. , Whitsel Eric A. , Wilson James G. , Horvath Steve , Jaiswal Siddhartha ,   the NHLBI Trans‐Omics for Precision Medicine (TOPMed) Consortium
Published: June 2021

AbstractClonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA‐methylation modifying enzymes DNMT3A or TET2. We used DNA‐methylation array and whole‐genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.31 years (GrimAge, p < 8.6 × 10−7) to 3.08 years (EEAA, p < 3.7 × 10−18). Mutations in most CHIP genes except DNA‐damage response genes were associated with increases in several measures of age acceleration. CHIP carriers with mutations in multiple genes had the largest increases in age acceleration and decrease in estimated telomere length. Finally, we found that ~40% of CHIP carriers had acceleration >0 in both Hannum and GrimAge (referred to as AgeAccelHG+). This group was at high risk of all‐cause mortality (hazard ratio 2.90, p < 4.1 × 10−8) and coronary heart disease (CHD) (hazard ratio 3.24, p < 9.3 × 10−6) compared to those who were CHIP−/AgeAccelHG−. In contrast, the other ~60% of CHIP carriers who were AgeAccelHG− were not at increased risk of these outcomes. In summary, CHIP is strongly linked to age acceleration in multiple clocks, and the combination of CHIP and epigenetic aging may be used to identify a population at high risk for adverse outcomes and who may be a target for clinical interventions.
Inhibition of AMPA receptors (AMPARs) containing transmembrane AMPAR regulatory protein γ‐8 with JNJ‐55511118 shows preclinical efficacy in reducing chronic repetitive alcohol self‐administration
Authors: Hoffman Jessica L. , Faccidomo Sara , Saunders Briana L. , Taylor Seth M. , Kim Michelle , Hodge Clyde W. 
Published: June 2021

AbstractBackgroundA prominent therapeutic indication for alcohol use disorder (AUD) is reduction in chronic repetitive alcohol use. Glutamate α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors (AMPARs) regulate chronic alcohol self‐administration in preclinical models. Recent evidence indicates that the expression and function of AMPARs require the transmembrane AMPAR regulatory protein γ‐8 (TARP γ‐8). This study evaluated the preclinical efficacy of JNJ‐55511118, a novel, selective, high‐affinity inhibitor of TARP γ‐8‐bound AMPARs, in reducing chronic operant alcohol self‐administration.MethodsSeparate groups of male and female C57BL/6J mice (n = 8/sex/group) were trained to lever press for sweetened alcohol (9% v/v + sucrose 2% w/v) or sucrose only (2% w/v) in operant conditioning chambers using an FR‐4 schedule of reinforcement. After a 40‐day baseline, JNJ‐55511118 (0, 1, and 10 mg/kg, p.o.) was administered in randomized order 1 h before self‐administration sessions. Parameters of operant behavior including response rate, total reinforcers, and head entries in the drinking troughs were computer recorded.ResultsDuring baseline, responding to alcohol, but not sucrose, was greater in female than male mice. In male mice, both doses of JNJ‐55511118 decreased multiple parameters of alcohol self‐administration but did not reduce behavior‐matched sucrose‐only self‐administration. JNJ‐55511118 had no effect on sweetened alcohol or sucrose self‐administration in female mice. Subsequent tests of motor function showed that the lowest effective dose of JNJ‐55511118 (1 mg/kg) had no effect on open‐field activity in male mice.ConclusionsThis study shows for the first time that TARP γ‐8‐bound AMPARs regulate a behavioral pathology associated with addiction. The preclinical efficacy of JNJ‐55511118 in reducing alcohol self‐administration in male mice suggests that inhibition of TARP γ‐8‐bound AMPARs is a novel and highly significant neural target for developing medications to treat AUD and other forms of addiction.
Impacts of Canada's cannabis legalization on police‐reported crime among youth: early evidence
Authors: Callaghan Russell C. , Vander Heiden Julia , Sanches Marcos , Asbridge Mark , Hathaway Andrew , Kish Stephen J. 
Published: June 2021

AbstractAimsCanada's 2018 Cannabis Act allows youth (age 12–17 years) to possess up to 5 g of dried cannabis (or equivalent) for personal consumption/sharing. This study assessed whether the Cannabis Act was associated with changes in police‐reported cannabis offences among youth in Canada.DesignTime series model using national daily criminal incident data from January 1, 2015–December 31, 2018 from the Canadian Uniform Crime Reporting Survey (UCR‐2). Seasonal autoregressive integrated moving average time series models, stratified by sex, assessed the relations between legalization and youth cannabis‐related offences.SettingCanada, 2015–2018.CasesPolice‐reported cannabis‐related offenses among youth age 12–17 years (male, n = 32 178; female, n = 9001).MeasurementsOutcomes: police‐reported cannabis‐related crimes, property crimes, and violent crimes. Covariate: calendar‐month.FindingsFor females, legalization was associated with a step‐effect decrease of 4.56 (95% confidence interval [CI] = 3.32, 5.81; P < 0.001) police‐reported cannabis‐related criminal offences per day, an effect equivalent to a 64.6% (standard error [SE] = 33.5%) reduction. For males, legalization was associated with a drop of 12.73 (95% CI = 8.82, 16.64; P < 0.001) cannabis‐related offences per day, equaling a decrease of 57.7% (SE = 22.6%). Results were inconclusive as to whether there were associations between cannabis legalization and patterns of property crimes or violent crimes.ConclusionsImplementation of the Cannabis Act in Canada in 2018 appears to have been associated with decreases of 55%–65% in cannabis‐related crimes among male and female youth.
Origin and population structure of Brazilian hair sheep breeds
Authors: Paim T. P. , Paiva S. R. , de Toledo N. M. , Yamaghishi M. B. , Carneiro P. L. S. , Facó O. , de Araújo A. M. , Azevedo H. C. , Caetano A. R. , Braga R. M. , McManus C. 
Published: June 2021

SummaryBrazilian hair sheep constitute a genetic diversity hotspot. These animals are found in the harsh environments of the Brazilian Northwest (semi‐arid) region. Genotypes (50K SNP chip) from seven Brazilian sheep breeds (five hair and two coarse wool types) and 87 worldwide breeds were used to test for population structure, admixture and genetic diversity. Moreover, phylogenetic trees evaluating migration events between genetic groups were built. Brazilian Somali, a fat‐tailed breed, had a close relationship with East African breeds and clustered distinctly from other Brazilian breeds. Brazilian Blackbelly and Barbados Blackbelly had a close relationship. The Morada Nova breed did not show close relationships with European or African breeds, revealing a single migration event from an Algerian hair breed. Brazilian Fat‐tail and Morada Nova share a common ancestor, but the former showed introgressions from Brazilian Somali and Afrikaner breeds, explaining the fat‐tail phenotype. The Santa Inês breed received a substantial contribution from Brazilian Bergamasca and showed an admixed origin with recent introgressions from other breeds, mainly from Suffolk. Furthermore, Brazilian Somali and Brazilian Fat‐tail are the most endangered sheep genetic resources in Brazil and should be the focus forex situconservation programs. In conclusion, Brazilian hair sheep show an African origin and are characterized by diverse genetic composition, reinforcing the need for conservation of these genetic resources, and at the same time, this highly diverse group has variability that can be used in breeding programs.
Serum and intratesticular inhibin B, AMH, and spermatogonial numbers in trans women at gender‐confirming surgery: An observational study
Authors: Schneider Florian , Dabel Jennifer , Sandhowe‐Klaverkamp Reinhild , Neuhaus Nina , Schlatt Stefan , Kliesch Sabine , Wistuba Joachim 
Published: June 2021

AbstractBackgroundAnti‐Müllerian hormone and inhibin B are produced by Sertoli cells. Anti‐Müllerian hormone secretion indicates an immature Sertoli cell state. Inhibin B serves as a marker of male fertility. Identification of markers reflecting the presence of germ cells is of particular relevance in trans persons undergoing gender‐affirming hormone therapy in order to offer individualized fertility preservation methods.ObjectivesSerum and intratesticular inhibin B and anti‐Müllerian hormone values were assessed and related to clinical features, laboratory values, and germ cell numbers.Materials and methodsTwenty‐two trans women from three clinics were included. As gender‐affirming hormone therapy, 10–12.5 mg of cyproterone acetate plus estrogens were administered. Height, weight, age, medication, and treatment duration were inquired by questionnaires. Serum luteinizing hormone, follicle‐stimulating hormone, testosterone, and estradiol were measured by immuno‐assays. Serum and intratesticular inhibin B and anti‐Müllerian hormone were measured by commercially available ELISAs. Spermatogonia were quantified as spermatogonia per cubic millimeter testicular tissue applying a morphometric analysis of two independent testicular cross‐sections per individual after MAGEA4 immunostaining.ResultsPatients with high inhibin B levels presented with a higher number of spermatogonia (*p < 0.05). Furthermore, mean serum inhibin B was associated with low age (*p < 0.05), low follicle‐stimulating hormone (*p < 0.05), and low testosterone (*p < 0.05). Serum anti‐Müllerian hormone, however, was not related to spermatogonial numbers. It correlated with high testosterone (*p < 0.05) and high follicle‐stimulating hormone (*p < 0.05) only. High intratesticular inhibin B was accompanied by high luteinizing hormone (*p < 0.05), high follicle‐stimulating hormone (**p < 0.01), and high testosterone levels (**p < 0.01). Higher the intratesticular anti‐Müllerian hormone levels, the longer gender‐affirming hormone therapy was administered (*p < 0.05).Discussion and conclusionSerum inhibin B levels indicate the presence of spermatogonia, whereas anti‐Müllerian hormone seems not to be a reliable marker concerning germ cell abundance.
The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age‐related macular degeneration long‐term treated in real world
Authors: Llorente‐González Sara , Hernandez Maria , González‐Zamora Jorge , Bilbao‐Malavé Valentina , Fernández‐Robredo Patricia , Saenz‐de‐Viteri Manuel , Barrio‐Barrio Jesús , Rodríguez‐Cid María José , Donate Juan , Ascaso Francisco J. , Gómez‐Ramírez Ana M. , Araiz Javier , Armadá Félix , Ruiz‐Moreno Óscar , Recalde Sergio , García‐Layana Alfredo ,   Spanish AMD group
Published: June 2021

AbstractPurposeTo assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age‐related macular degeneration (nAMD) receiving long‐term treatment in the real world.MethodsAn ambispective 36‐month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best‐corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed.ResultsAfter 36 months of follow‐up and an average of 13.8 anti‐VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85–12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09–3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23–0.71) and its progression (OR = 0.44, 95% CI = 0.26–0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14–0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36‐month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29–0.81) and its progression (OR = 0.50, 95% CI = 0.31–0.81).ConclusionAtrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.