bluuebunny/crossref_metadata_2025_split huggingface dataset:
GW117: A novel serotonin (5‐HT2C) receptor antagonist and melatonin (MT1/MT2) receptor agonist with potential antidepressant‐like activity in rodents
Authors: Gao Nana , Zheng Wei , Murezati Tiliwaerde , Gu Wei , Li Xiaorong , Jin Zengliang 
Published: March 2021

AbstractAimsTo evaluate the antidepressant‐like effect of compound GW117 in rodents using in vitro binding and uptake assays as well in vivo behavioral tests.MethodsWe investigated the target profile of GW117 using [35S]‐GTPγS and [3H]PIP binding. Using the forced swimming test and chronic unpredictable stress in rats, tail suspension test in mice and rats, and learned helplessness model in mice, we further revealed the antidepressant‐like and anxiolytic‐like effects of GW117.ResultsThe current study suggests that GW117 displays serotonin 2C (5‐HT2C) receptor antagonist and melatonin type 1 and 2 (MT1/MT2) receptor agonist properties, as well as evident antidepressant and anxiolytic effects.ConclusionThese data suggest that GW117 is probably a potent antidepressant.
Beyond exposure‐response: A tutorial on statistical considerations in dose‐ranging studies
Authors: Laird Glen , Xu Lei , Liu Meng , Liu Jin 
Published: March 2021

AbstractDose‐ranging studies are a crucial part of the phase II drug development process. They complement the understanding gained from exposure‐response analyses. However, the statistical design issues related to dose‐ranging studies are not always keenly understood and a poorly designed study can be costly for later development. In this tutorial, we review five key statistical principles in designing such a study. We also describe some popular statistical approaches, including pairwise comparison, modeling, and Multiple Comparison Procedure modeling in the context of principles.
Cellular studies of the two main isoforms of human d‐aspartate oxidase
Authors: Rabattoni Valentina , Pollegioni Loredano , Tedeschi Gabriella , Maffioli Elisa , Sacchi Silvia 
Published: March 2021

Human d‐aspartate oxidase (hDASPO) is a FAD‐dependent enzyme responsible for the degradation of d‐aspartate (d‐Asp). In the mammalian central nervous system, d‐Asp behaves as a classical neurotransmitter, it is thought to be involved in neural development, brain morphology and behavior, and appears to be involved in several pathological states, such as schizophrenia and Alzheimer's disease. Apparently, the human DDO gene produces alternative transcripts encoding for three putative hDASPO isoforms, constituted by 341 (the ‘canonical’ form), 369, and 282 amino acids. Despite the increasing interest in hDASPO and its physiological role, little is known about these different isoforms. Here, the additional N‐terminal peptide present in the hDASPO_369 isoform only has been identified in hippocampus of Alzheimer’s disease female patients, while peptides corresponding to the remaining part of the protein were present in samples from male and female healthy controls and Alzheimer’s disease patients. The hDASPO_369 isoform was largely expressed in E. coli as insoluble protein, hampering with its biochemical characterization. Furthermore, we generated U87 human glioblastoma cell clones stably expressing hDASPO_341 and, for the first time, hDASPO_369 isoforms; the latter protein showed a lower expression compared with the canonical isoform. Both protein isoforms are active (showing similar kinetic properties), localize to the peroxisomes, are very stable (a half‐life of approximately 100 h has been estimated), and are primarily degraded through the ubiquitin–proteasome system. These studies shed light on the properties of hDASPO isoforms with the final aim to clarify the mechanisms controlling brain levels of the neuromodulator d‐Asp.
Global patterns of forest autotrophic carbon fluxes
Authors: Banbury Morgan Rebecca , Herrmann Valentine , Kunert Norbert , Bond‐Lamberty Ben , Muller‐Landau Helene C. , Anderson‐Teixeira Kristina J. 
Published: March 2021

AbstractCarbon (C) fixation, allocation, and metabolism by trees set the basis for energy and material flows in forest ecosystems and define their interactions with Earth's changing climate. However, while many studies have considered variation in productivity with latitude and climate, we lack a cohesive synthesis on how forest carbon fluxes vary globally with respect to climate and one another. Here, we draw upon 1,319 records from the Global Forest Carbon Database, representing all major forest types and the nine most significant autotrophic carbon fluxes, to comprehensively review how annual C cycling in mature, undisturbed forests varies with latitude and climate on a global scale. Across all flux variables analyzed, rates of C cycling decreased continuously with absolute latitude—a finding that confirms multiple previous studies and contradicts the idea that net primary productivity of temperate forests rivals that of tropical forests. C flux variables generally displayed similar trends across latitude and multiple climate variables, with no differences in allocation detected at this global scale. Temperature variables in general, and mean annual temperature or temperature seasonality in particular, were the best single predictors of C flux, explaining 19%–71% of variation in the C fluxes analyzed. The effects of temperature were modified by moisture availability, with C flux reduced under hot and dry conditions and sometimes under very high precipitation. Annual C fluxes increased with growing season length and were also influenced by growing season climate. These findings clarify how forest C flux varies with latitude and climate on a global scale. In an era when forests will play a critical yet uncertain role in shaping Earth's rapidly changing climate, our synthesis provides a foundation for understanding global patterns in forest C cycling.
Pharmacokinetic implications of dosing emicizumab based on vial size: A simulation study
Authors: Yu Jacky K. , Iorio Alfonso , Chelle Pierre , Edginton Andrea N. 
Published: March 2021

AbstractIntroductionEmicizumab is dosed as mg/kg and, according to the label, any unused drug left in the vial(s) must be discarded, thereby wasting expensive resources. The aim of this study was to use population pharmacokinetics to illustrate the implications of changing the dosing interval to avoid wastage.MethodsWe used a previously published emicizumab PopPK model after extending its validation to children. We simulated PK parameters for labelled dosing regimens and for regimens using full vials with infusion frequency varied to keep the steady‐state drug concentration unchanged. Cost and drug savings were calculated.ResultsThe model evaluation was successful. When rounding up, the average individual below 53, 47 and 39 has a time‐to‐trough increase of up to 5.7, 7.9 and 5.8 days for the QW, Q2 W and Q4 W regimen, respectively. This resulted in an annual cost reduction of up to $173,136, $75,747 and $61,319 USD per patient. At higher body weights, rounding down the dose to the nearest vial resulted in negligible changes in the steady state concentration and cost savings of up to $93,781, $46,891 and $23,446 USD per patient, respectively.ConclusionIndividuals with a lower body weight may benefit from increasing dose intervals and rounding up dose up to the nearest vial, and individuals with a higher body weight from maintaining the injection frequency and rounding dose down to the nearest vial without significant change in emicizumab levels. Administering the entire vial may result in a reduction of vials used annually and potential cost savings.
Innovative methods for involving people with dementia and carers in the policymaking process
Authors: Keogh Fiona , Carney Patricia , O’Shea Eamon 
Published: March 2021

AbstractBackgroundThere are few examples of public patient involvement in policymaking for groups whose ability to participate may be affected by a disability, particularly for people with dementia and their family carers. Principles of engagement and inclusion in democratic processes are as important for these groups as other citizens. We used two innovative methods to increase involvement of people with dementia and family carers in the policymaking process in Ireland, specifically in relation to impending legislation on home care.MethodA Policy Café was co‐produced with people with dementia using a World Café methodology. A Carer's Assembly was co‐produced with caregivers of people with dementia using a citizen's assembly model.ResultsTen people with dementia discussed policy developments they wanted to see implemented in relation to diagnosis and home care. Twenty‐eight dementia caregivers prioritized four topics: home care; respite services; psychosocial supports; and financial supports. Film and illustrations were used to create accessible messages for policy‐makers to inform their decision making.DiscussionInvolving people with dementia and carers in policy development requires time and creativity to facilitate and maximize their involvement. Co‐production is essential to ensure the priorities of participants are identified, expressed and communicated effectively. A cumulative sequence of events and messages can generate significant engagement with policy‐makers. Policy‐makers need to hear the direct and authentic voice of people with dementia and carers when faced with important policy decisions.Patient or public contributionPeople with dementia and carers were involved in study design, data analysis and presentation.
Comparison of losartan and amlodipine effects on the outcomes of patient with COVID‐19 and primary hypertension: A randomised clinical trial
Authors: Nouri‐Vaskeh Masoud , Kalami Niusha , Zand Ramin , Soroureddin Zahra , Varshochi Mojtaba , Ansarin Khalil , Rezaee Haleh , Taghizadieh Ali , Sadeghi Armin , Ahangari Maleki Masoud , Esmailnajad Azam , Saleh Parviz , Haghdoost Mehdi , Maleki Mehdi , Sharifi Akbar 
Published: March 2021

AbstractBackgroundControversy exists regarding the drug selection in hypertension (HTN) management in patients with COVID‐19. This study aimed to compare the effects of losartan and amlodipine in patients with primary HTN and COVID‐19.MethodsIn this randomised clinical trial, hospitalised patients with COVID‐19 and primary HTN were enrolled in the study. One arm received losartan, 25 mg, twice a day and the other arm received amlodipine, 5 mg per day for 2 weeks. The main outcomes were compare 30‐day mortality rate and length of hospital stay.ResultsThe mean age of patients treated with losartan (N = 41) and amlodipine (N = 39) was 67.3 ± 14.8 and 60.1 ± 17.3 years, respectively (P value = .068). The length of hospital stay in losartan and amlodipine groups was 4.57 ± 2.59 and 7.30 ± 8.70 days, respectively (P value = .085). Also, the length of ICU admission in losartan and amlodipine group was 7.13 ± 5.99 and 7.15 ± 9.95 days, respectively (P value = .994). The 30‐day mortality was two and five patients in losartan and amlodipine groups, respectively (P value = .241).ConclusionsThere was no priority in losartan or amlodipine administration in COVID‐19 patients with primary HTN in decreasing mortality rate, hospital and ICU length stay. Further studies need to clarify the first‐line anti‐HTN medications in COVID‐19.
Latent profile analysis of ethical consumers in the United States and Malaysia
Authors: Shim KyuJin , Cho Hichang 
Published: March 2021

AbstractThrough using Moral Foundations Theory (MFT) and the Latent Profile Analysis (LPA) method, this study proposes a new approach to ethical consumer categorization. Based on a survey using national survey data of more than 1,000 people in the United States and Malaysia, this study found three common ethical consumer groups based on ethical sensitivity in both countries—moral enthusiast, moral interested, and moral indifferent. In addition to the aforementioned commonalities, we found national differences in consumer profiles: the U.S. sample also shows a moral progressivist group inclined to liberal ethics, while the Malaysia sample shows a moral intuitionist group with a relativistic approach in ethical decision making. The results indicate that ethical consumer profiling based on MFT has a sufficient level of criterion validity as it helps predict moral outrage, pro‐business attitudes, and boycott intentions in response to corporate irresponsibility. The study also demonstrates cross‐cultural differences in moral foundations and moral judgments in the context of ethical consumerism and corporate social irresponsibility.
The prognostic significance of single‐nucleotide polymorphism array‐based whole‐genome analysis and uniparental disomy in myelodysplastic syndrome
Authors: Ou Yang , Yang Yan , Yu Hongbin , Zhang Xin , Liu Min , Wu Yu 
Published: March 2021

AbstractIntroductionMyelodysplastic syndrome (MDS) is a group of heterogeneous hematological diseases characterized by ineffective hematopoiesis and dysplastic morphology. Single nucleotide polymorphism array (SNP‐A)‐based whole genome analysis has a much higher resolution for chromosomal alterations when compared with conventional cytogenetic tools. In the present study, we evaluated the diagnostic value and prognostic significance of SNP‐A in MDS patients with normal karyotypes.MethodsA total of 127 patients with MDS and myeloproliferative neoplasms or acute myeloid leukemia with myelodysplasia‐related changes were included in our study. The advantages and disadvantages of SNP‐A were compared with those of traditional metaphase cytogenetic analysis (MC). The Kaplan‐Meier analysis and COX regression analysis were used to investigate the prognostic value of SNP‐A and uniparental disomy (UPD) in MDS patients with normal karyotype. Furthermore, the chromosomal abnormalities detected by SNP‐A in patients with specific gene mutations were explored.ResultsSNP‐A was more sensitive toward meaningful chromosomal aberrations (58.2% vs 36.9%; P < .05) than MC. Among the patients with normal karyotype, those who were detected with new chromosomal abnormalities via SNP‐A presented with inferior survival compared with those without the abnormalities (P = .003). Additionally, the presence of UPD was an independent prognostic factor in patients with normal karyotype (P = .01). TP53 and RUNX1 mutations often occurred with abnormalities in chromosomes 17p and 21q, respectively.ConclusionsCompared with MC, SNP‐A capable of detecting UPD can offer more diagnostic and prognostic information; TP53 and RUNX1 gene mutations are often accompanied by abnormalities in their chromosomes (17p, 22q).
Temporal trends in the burden of heart failure
Authors: Chan Daniel Z. L. , Kerr Andrew J. , Doughty Rob N. 
Published: March 2021

AbstractHeart failure is a common healthcare problem associated with high morbidity and mortality. The burden of heart failure is changing; increases secondary to an ageing population may be offset by improved primary cardiovascular prevention and advances in heart failure therapies. In this review, we evaluate recent international trends in heart failure incidence, morbidity and mortality. Although the age‐standardised incidence of heart failure has been decreasing since 2000, the incidence in those age groups <55 years is increasing with patients being diagnosed at younger ages. Despite improvements in therapies for heart failure, prognosis still remains poor with up to one‐third of patients not surviving beyond 1 year following diagnosis and no improvements in mortality over the past 10 years. The case‐mix of heart failure patients is changing with a greater proportion having non‐ischaemic aetiology and preserved ejection fraction, and a higher prevalence of non‐cardiovascular comorbidity and mortality.
Indigenous cultural re‐presentation and re‐affirmation: The case of Māori IT professionals
Authors: Díaz Andrade Antonio , Techatassanasoontorn Angsana A. , Singh Harminder , Staniland Nimbus 
Published: March 2021

AbstractWestern worldviews dominate the information systems (IS) literature, accepted and taken for granted as the natural way of doing things. While diversity in terms of gender and ethnicity has been studied in the IS field, there is scant research on the experiences of Indigenous information technology (IT) professionals. This study uses narrative inquiry to provide temporal, contextualised accounts of IT professional experiences from the Indigenous (Māori) community in Aotearoa, New Zealand. These accounts demonstrate how participants actively draw from their culture to enact their professional activities. We identify three cultural elements that differentiate the practices of Māori IT professionals from Western approaches that dominate the IS literature: whakapapa (genealogical connections), tikanga (customary traditions) and tino rangatiratanga (collective cultural determination). Further, we theorise how Indigenous IT professionals capitalise on the re‐presentational power of digital artefacts as a vehicle for cultural re‐affirmation to project their Indigenous identity in contemporary society. Our findings are useful for attempts to enhance Indigenous representation in the IT workforce and for designing systems and artefacts that are relevant to and inclusive for Indigenous communities.
2D‐HARECXS analysis of dopant and oxygen vacancy sites in Al‐doped yttrium titanate
Authors: Ohtsuka Masahiro , Oda Kenji , Tanaka Makoto , Kitaoka Satoshi , Muto Shunsuke 
Published: March 2021

AbstractA Y2Ti2O7/Al2O3 multilayer, exhibiting high thermal reflectivity and oxidation resistivity, holds potential as a functional surface coating for advanced gas turbine blades. Slight Al doping of Y2Ti2O7 has been found to significantly improve the structural stability of the multilayer, the detailed mechanism of which remains unclear. Hence, we examined the site occupancies of doped Al using high‐angular resolution electron channeling X‐ray spectroscopy with two‐dimensional rocking of the incident electron beam. A statistical linear regression analysis of a set of observed ionization channeling patterns (ICPs) of fluorescent X‐rays quantitatively confirmed that Al3+ preferentially occupied the Ti4+ site, rather than the Y3+ site, because of the large difference in the ionic radii of Al3+ and Y3+. Furthermore, the comparison of theoretical and experimental X‐ray ICPs showed that oxygen vacancies VO were introduced at the 48f site, the first‐nearest neighbor of the Ti site, which was consistent with the hypothesis that oxygen vacancies compensate for the local charge imbalance associated with preferential substitution of Al3+ for Ti4+. Our findings can aid in improving the thermal properties of environmental barrier coatings applied to advanced jet engines and also demonstrate the utility of beam‐rocking schemes for investigating dopant effects in various functional materials.
Triglyceride to high‐density lipoprotein cholesterol ratio variability and incident diabetes: A 7‐year prospective study in a Chinese population
Authors: Cai Zefeng , Chen Zekai , Fang Wei , Li Weijian , Huang Zegui , Wang Xianxuan , Chen Guanzhi , Wu Weiqiang , Chen Zhichao , Wu Shouling , Chen Youren 
Published: March 2021

AbstractAims/IntroductionThe correlation between triglyceride to high‐density lipoprotein cholesterol (TG/HDL‐C) ratio variability and incident diabetes has not been fully elucidated. We aimed to characterize the relationship between TG/HDL‐C ratio variability and new‐onset diabetes in Chinese adults.Materials and MethodsA total of 45,911 patients with three TG and HDL measurements between 2006 and 2011 were enrolled. Average real variability (ARV) were used to evaluate variability, and participants were grouped according to tertiles of TG/HDL‐ARV.ResultsThere were 3,724 cases of incident diabetes mellitus during the observation period (6.24 ± 1.2 years). The 7‐year cumulative incidences of diabetes mellitus in tertiles 1, 2 and 3 were 6.13%, 8.09% and 11.77%, respectively. New‐onset diabetes increased with the tertiles of TG/HDL‐ARV. This association was further confirmed after adjustment for mean TG/HDL‐C ratio, TG/HDL‐C ratio change slope, fasting plasma glucose variability (ARV) and other traditional risk factors for diabetes, the hazard ratio value for incident diabetes was 1.38 (1.25–1.50) for the highest tertile, and risk of diabetes increases by 4% with a one standard deviation increase in TG/HDL‐C ratio variability. Restricted cubic splines showed a dose–response relationship between TG/HDL‐C ratio variability and incident diabetes. Similar results were obtained in various subgroup and sensitivity analyses.ConclusionsHigh TG/HDL‐C variability was associated with a higher risk of diabetes in Chinese adults, independent of the direction of TG/HDL‐C variability.
Cost‐of‐illness of atopic dermatitis in Germany: data from dermatology routine care
Authors: Mohr N. , Naatz M. , Zeervi L. , Langenbruch A. , Bieber T. , Werfel T. , Wollenberg A. , Augustin M. 
Published: March 2021

AbstractBackgroundProgress in the management of atopic dermatitis (AD) and the recent introduction of the first biologic have raised interest in the costs of treating AD.ObjectivesSince there is a lack of recent data, the objective of this study was to determine the annual costs of adults with AD from the societal perspective.MethodsA nationwide cross‐sectional study was conducted in 111 dermatological offices under routine conditions. Cost parameters were collected with a standardised questionnaire on disease‐related costs. This questionnaire allows the determination of costs for systemic and topical treatment, outpatient and inpatient visits, rehabilitation stays and travel costs. Direct costs were determined for the statutory health insurance (SHI) and for the patients (out‐of‐pocket costs). Societal costs also included the indirect costs due to incapacity to work. Costs were calculated for all severity grades and further stratified by mild and moderate‐to‐severe AD.ResultsFrom August 2017 to June 2019, N = 1291 adult patients from all over Germany were included. The total annual costs in the group with all severity grades (n = 706) amounted to € 3616 ± € 6452 (median € 874) per patient. For patients with mild AD (n = 367), the annual costs were € 1466 ± € 3029 (median € 551) per patient, while they were € 5229 ± € 7538 (median € 1791) for patients with moderate‐to‐severe AD (n = 682). The total economic burden for treating adult patients with AD in Germany is estimated at more than € 2.2 billion.ConclusionsIn total, the data from this study show that compared to for example psoriasis, AD has a moderate level of costs‐of‐illness in Germany. The approval of new therapies is expected to lead to markedly more resource utilisation in the next years.