bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, pharmacokinetics and pharmacodynamics of HTL0009936, a selective muscarinic M1‐acetylcholine receptor agonist: A randomized cross‐over trial
Authors: Bakker Charlotte , Prins Samantha , Liptrot Jan , Hart Ellen P. , Klaassen Erica S. , Brown Giles A. , Brown Alastair , Congreve Miles , Weir Malcolm , Marshall Fiona H. , Stevens Jasper , Cross David M. , Tasker Tim , Nathan Pradeep J. , Groeneveld Geert Jan 
Published: April 2021

AimsHTL0009936 is a selective M1 muscarinic receptor agonist in development for cognitive dysfunction in Alzheimer's disease. Safety, tolerability and pharmacokinetics and exploratory pharmacodynamic effects of HTL0009936 administered by continuous IV infusion at steady state were investigated in elderly subjects with below average cognitive functioning (BACF).MethodsPart A was a four‐treatment open label sequential study in healthy elderly investigating 10–83 mg HTL0009936 (IV) and a 24 mg HTL0009936 single oral dose. Part B was a five‐treatment randomized, double‐blind, placebo and physostigmine controlled cross‐over study with IV HTL0009936 in elderly subjects with BACF. Pharmacodynamic assessments were performed using neurocognitive and electrophysiological tests.ResultsPharmacokinetics of HTL0009936 showed dose‐proportional increases in exposure with a mean half‐life of 2.4 hours. HTL0009936 was well‐tolerated with transient dose‐related adverse events (AEs). Small increases in mean systolic blood pressure of 7.12 mmHg (95% CI [3.99–10.24]) and in diastolic of 5.32 mmHg (95% CI [3.18–7.47]) were noted at the highest dose in part B. Overall, there was suggestive, but no definitive, positive or negative pharmacodynamic effects. Statistically significant effects were observed on P300 with HTL0009936 and adaptive tracking with physostigmine.ConclusionsHTL0009936 showed well‐characterized pharmacokinetics and single doses were safe and generally well‐tolerated in healthy elderly subjects. Due to physostigmine tolerability issues and subject burden, the study design was changed and some pharmacodynamic assessments (neurocognitive) were performed at suboptimal drug exposures. Therefore no clear conclusions can be made on pharmacodynamic effects of HTL0009936, although an effect on P300 is suggestive of central target engagement.
Presuming incapacity in anorexia nervosa is indefensible: A reply to Ip
Authors: Miller Tate Alex James 
Published: April 2021

AbstractEric C. Ip has recently argued that seriously anorexic service users ought to be assumed to be legally incapacitous to refuse life‐saving artificial nutrition unless they can demonstrate otherwise, reversing the ordinary legal presumption in place to protect patients’ liberty and values. In this response, I argue against this proposal on two grounds. Firstly, the proposal is wrongfully discriminatory; it would expose service users to serious harm, and wrong them in numerous ways, on the basis of their diagnosis alone, without significantly benefitting them in any way relative to the status quo. Secondly, he is unable to show that a large majority of such service users actually are incapacitous to refuse life‐saving artificial nutrition. This means that his proposal would likely involve declaring a large number of actually capacitous patients to be incapacitous, without even the requirement of a formal assessment, and burdening them with the responsibility of proving their clinical team wrong if they wish to avoid deprivation of liberty and/or compelled treatment. Given this, his proposal is indefensible.
A Multiple‐Memory Systems Framework for Examining Attention and Memory Interactions in Infancy
Authors: Amso Dima , Kirkham Natasha 
Published: April 2021

AbstractVisual attention both guides and is guided by learning and memory systems. In this article, we use a multiple‐memory systems framework to examine the interplay between attention and memory that begins in early postnatal life. We review how attention and memory interact to support infant development with respect to perceptual learning about objects and features, item‐in‐context spatial memory, and reinforcement and reward learning. We argue that the multiple‐memory systems approach offers a useful organizational structure for research on interactions between attention and memory.
Biallelic start loss variant, c.1A > G in GCSH is associated with variant nonketotic hyperglycinemia
Authors: Majethia Purvi , Somashekar Puneeth Hirivate , Hebbar Malavika , Kadavigere Rajagopal , Praveen Balike Krishna , Girisha Katta Mohan , Shukla Anju 
Published: April 2021

AbstractThe glycine cleavage system H protein (GCSH) is an integral part of the glycine cleavage system with its additional involvement in the synthesis and transport of lipoic acid. We hypothesize that pathogenic variants in GCSH can cause variant nonketotic hyperglycinemia (NKH), a heterogeneous group of disorders with findings resembling a combination of severe NKH (elevated levels of glycine in plasma and CSF, progressive lethargy, seizures, severe hypotonia, no developmental progress, early death) and mitochondriopathies (lactic acidosis, leukoencephalopathy and Leigh‐like lesions on MRI). We herein report three individuals from two unrelated Indian families with clinical, biochemical, and radiological findings of variant NKH, harboring a biallelic start loss variant, c.1A > G in GCSH.
Autonomy, Centrality, and Persistence in Place: The Indigenous Movement and the Right to the City in Quito
Authors: Rayner Jeremy 
Published: April 2021

AbstractThis article draws on ethnography with active supporters of the comunas (communes) in Quito to critically engage with the theory and politics of the right to the city. Communal activists—mostly affiliated with the Indigenous movement—forcefully claim rights to the democratic production and appropriation of space advocated by right to the city theorists, as they promote communal self‐management and the authority of communal assemblies over urbanization processes. At the same time, they have had little use for their constitutionally guaranteed right to the city. In carefully laying out the points of convergence between Lefebvrian right to the city theory and communal struggles, I also identify its limits and contradictions, especially: (1) the tension between “the collective power to reshape the process of urbanization” and the fixed forms and meanings of “the city,” and (2) the tension between achieving the “right to centrality” through promoting participation in a concentrated urban center or through the multiplication of centers. A critical theory of urbanization should account for these tensions and for the diversity of political responses to them.
Live wild animal exports to supply the exotic pet trade: A case study from Togo using publicly available social media data
Authors: Harrington Lauren A. , Auliya Mark , Eckman Harry , Harrington Alix P. , Macdonald David W. , D'Cruze Neil 
Published: April 2021

AbstractExotic pet supply is a key, predominantly legal, component of global wildlife trade, but few studies have quantified its diversity or global reach. Here, using information extracted from the public (open) Facebook accounts of two wildlife exporters in Togo, West Africa, we identified at least 200 species, predominantly reptiles, but also mammals, birds, amphibians and invertebrates, advertised as available for sale and export, between the years 2016 and 2020. Of the animals identified, several hundred, possibly several thousand, individuals were shipped, at least monthly, to North America, Europe, Asia, and elsewhere in Africa, via a number of major airlines. Among the vertebrates observed, approximately one‐third had not yet been evaluated on the IUCN Red list, and three quarters were not CITES‐listed (i.e., their trade was not regulated under this international treaty). The apparent lack of adequate monitoring of population status, disease, biological invasion, and animal welfare risks associated with this trade, as well as neglected taxa (e.g., invertebrates), has potential implications for environmental, public, and animal health. The findings of this case study suggest that a systematic review of social media activity could efficiently reveal significant insights into the otherwise undocumented global supply of exotic pets, directing legislators to aspects and areas where regulation is insufficient, and informing international and national policy change.
Predictors of development and persistence of musculoskeletal pain in community‐dwelling older people: A two‐year longitudinal study
Authors: Hirase Tatsuya , Okubo Yoshiro , Delbaere Kim , Menant Jasmine C , Lord Stephen R , Sturnieks Daina L 
Published: April 2021

AimThe aim of this prospective cohort study was to identify the predictors of the development and persistence of musculoskeletal pain (MSKP) in older people.MethodsParticipants comprised 431 community‐dwelling older people aged 70+ years. Demographic, anthropometric, balance, mobility, cognitive function, psychological status and physical activity level measures were obtained at baseline. Participants were asked about the presence of MSKP in the neck/back, hip, knee/leg and/or feet at baseline and two‐year follow‐up. Logistic regression analyses were performed to identify predictors of the development and persistence of MSKP at two‐year follow‐up.ResultsOf 179 participants who reported no MSKP at baseline, 84 (46.9%) reported MSKP at two‐year follow‐up, which was associated with a higher body mass index (odds ratio (OR) 1.10, 95% confidence interval (CI) 1.02–1.18), more reported depressive symptoms (OR 1.30, 95% CI 1.05–1.61) and lower physical activity levels (OR 0.92, 95% CI 0.84–1.00) at baseline. Of 252 participants who reported MSKP at baseline, 202 (80.2%) reported MSKP at follow‐up, which was associated with a slower 6‐m walking time (OR 1.27, 95% CI 1.08–1.49) and more reported depressive symptoms (OR 1.39, 95% CI 1.09–1.78). These associations remained significant after adjusting for age, sex, comorbidities and medication use.ConclusionsThis study suggests that higher body mass index, more depressive symptoms and less physical activity are predictors of developing MSKP, whereas slow gait speed and depressive symptoms are predictors of the persistence of MSKP among older people. The results highlight the importance of weight control, strategies to improve mental wellbeing and an active lifestyle for pain management among older people. Geriatr Gerontol Int 2021; 21: 519–524.
Emicizumab prophylaxis: Prospective longitudinal real‐world follow‐up and monitoring
Authors: Barg Assaf A. , Budnik Ivan , Avishai Einat , Brutman‐Barazani Tami , Bashari Dalia , Misgav Mudi , Lubetsky Aaron , Kuperman Amir A. , Livnat Tami , Kenet Gili 
Published: April 2021

AbstractIntroductionReal‐world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce.AimTo study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort.MethodsHA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled. Bleeding, adverse events and surgeries were documented. FVIII inhibitors, emicizumab levels and thrombin generation (TG) were sequentially measured.ResultsA total of 107 patients, including 58 children (whose median (IQR) age was 6 (1–11) years) with severe HA, composed the study cohort. Twenty‐nine per cent (31/107) of our HA patients had FVIII inhibitors. Patients were followed for a median of 67 weeks (up to 144 weeks). Fifty‐three patients, whose median follow‐up was 53 weeks, experienced zero bleeds. Most bleeds (94%) among children were trauma‐related, whereas 61% of adults sustained spontaneous joint bleeds. Four patients experienced major bleeds, with a fatal outcome in one infant, who also presented with central venous line thrombosis. No other serious adverse events were encountered. Seven patients have decided to stop emicizumab treatment for various reasons. Emicizumab plasma levels increased after emicizumab prophylaxis initiation, and values were maintained during follow‐up, in all but one patient, suspected of anti‐drug antibodies. A significant reduction of FVIII inhibitor levels was noted among inhibitor patients. TG was increased and sustained yet could not prognosticate bleeding risk.ConclusionEmicizumab prophylaxis was mostly well tolerated, although 50% of patients experienced breakthrough bleeds. Routine TG monitoring is not obligatory, and further studies are warranted in selected patient populations.
Cost‐analysis of opportunistic influenza vaccination in general medical inpatients
Authors: Darmaputra Daniel C. , Zaman Farzana Y. , Khu Yin Li , Nagalingam Vathy , Liew Danny , Aung Ar Kar 
Published: April 2021

AbstractInfluenza vaccination is an important preventative health measure in the elderly and those with medical comorbidities. It has been shown to reduce hospitalisations, cardiovascular and respiratory complications. A significant proportion of patients admitted to general medicine are eligible for opportunistic inpatient influenza vaccination. This study explores the cost‐effectiveness of such a strategy in reducing subsequent healthcare utilisation costs.
Three‐dimensional printing of zirconia scaffolds for load bearing applications: Study of the optimal fabrication conditions
Authors: Gaddam Anuraag , Brazete Daniela S. , Neto Ana S. , Nan Bo , Ferreira José M. F. 
Published: April 2021

AbstractYttria‐stabilized zirconia (YSZ) scaffolds with a planned macroporosity fraction of about 70% were fabricated by Robocasting from inks with high solid loadings. The effects of solids loading and the concentrations of processing additives on the flow behavior of the starting suspensions and the viscoelastic properties of the resulting inks were investigated aiming at optimizing the printing process. The shear thinning flow behavior of the starting suspensions containing 45‒48 vol% solids and dispersant concentrations varying within 0.2‒0.8 wt% could be well described by the four‐parameter Cross model. The flow behavior of the suspensions could be correlated with the interaction forces, and the ad‐layer thickness formed around the YSZ particles. Further adding suitable amounts of a binder and a coagulating agent enabled optimizing the viscoelastic properties of inks for 3D printing. Good shape retention was observed for inks with elastic modulus, G′ ≥ 10 MPa. The green scaffolds were dried, sintered at 1350°C, and then used for the assessment of porosity and mechanical properties under compression tests. The porous structures exhibit average compressive strength (σ) of ~70 MPa. Weibull statistics applied to σ data revealed good reliability of the process, which can be used to fabricate YSZ scaffolds for orthopedic applications.
Fermented foods: Availability, cost, ingredients, nutritional content and on‐pack claims
Authors: Whelan Kevin , Jones Nicola 
Published: April 2021

AbstractIntroductionFermented foods have been consumed for millennia and commercially‐produced variants are now available in the food supply. The present study aimed to investigate the availability, cost, ingredients, nutritional content and on‐pack claims of commercially‐available fermented foods in the UK.MethodsAll products from seven categories of commercially‐available fermented foods were systematically identified at eight national supermarket chains in the UK. Data were extracted from manufacturer and retailer websites and were compared between categories using a Kruskal–Wallis test and Fisher's exact test.ResultsIn total, 143 fermented foods were identified, with kombucha (41, 28.7%), kefir drinks (32, 22.4%), sauerkraut (22, 15.4%) and kefir yoghurts (21, 14.7%) being most common. The number of products sold at each retailer differed between categories (p = 0.016), and was greatest for kefir drink (median = 7.0, interquartile range [IQR] = 9.0), kombucha (median = 5.5, IQR = 11.5) and kefir yoghurts (median = 5.0, IQR = 8.5). Kombucha (£1.99 per serving) and kefir drinks (£1.26 per serving) were the most expensive fermented foods and sauerkraut (£0.66 per serving) and miso (£0.20 per serving) were the least expensive. Energy, fat, saturated fat, sugar, protein and salt content varied between fermented foods (p < 0.001). Nutrition claims were made on 72 (50.3%) products, the total number of cultures was labelled on 29 (20.3%), specific strains were named on 53 (37.1%) and bacteria‐related benefits were promoted on 39 (27.3%) products.ConclusionsCommercially‐produced fermented foods are widely available in the UK but are diverse in their cost, nutritional content, ingredients and use of on‐pack claims. Consumers should be aware of these variations given the limited evidence of functional benefits from controlled human trials.
The Endurance of Shareholder Value Maximization as the Preferred Corporate Objective
Authors: Inkpen Andrew C. , Sundaram Anant K. 
Published: April 2021

AbstractSundaram and Inkpen (2004a, 2004b) proposed shareholder value maximization (SVM) as the preferred corporate objective since it alone impels the firm to implement strategies that enhance outcomes for all stakeholders. Goranova and Ryan (2021) argue that three recent developments – common ownership, decoupling of owners from managers, and greater divergence in shareholder interests – call into question our SVM view. We dispute their arguments: (i) The developments they cite are overplayed in the literature, and may not matter much for SVM; (ii) To the extent they do matter, their concern is less about SVM’s relevance as corporate objective but more whether these developments bias decisions towards the short‐term. We do not disagree since, after all, Sundaram and Inkpen (2004a) is solely about SVM for the long‐term; (iii) If anything, Goranova and Ryan’s (2021) proposed solution of ‘strategic corporate governance’ can be viewed as an endorsement of the relevance and enduring primacy of SVM for the long‐term.
Is peripartum maternal fever alone a reliable predictor of neonatal sepsis? A single‐centre, retrospective cohort study
Authors: Gupta Soumya , Forbes‐Coe Amy , Rudd Donna , Kandasamy Yogavijayan 
Published: April 2021

AimTo determine the incidence rate of early‐onset neonatal sepsis (EONS) among term neonates (gestation greater than 37 weeks) admitted to the neonatal intensive care unit for suspected sepsis and the association of EONS with maternal fever (temperature greater than 38°C).MethodsA single‐centre retrospective cohort study of all term neonates (gestation >37 weeks) admitted to and treated in the neonatal unit at the Townsville University Hospital between March 2015 and March 2020. Neonatal sepsis was confirmed with positive neonatal blood culture. Data on neonatal birth/stay and maternal pregnancy were collected from the electronic medical records and neonatal database.ResultsData from 737 neonates who were admitted for treatment of EONS were analysed. Sixty % (426) reported maternal intrapartum fever, with 1.1% (5) of neonates developing blood culture‐proven sepsis. Forty % did not report intrapartum fever (311), with 3% (9) of neonates developing sepsis. As such, the sensitivity and specificity of maternal fever are 1.14% and 97%, respectively. The positive predictive value was 35.7%, and the negative predictive value was 40.1%. Fourteen neonates developed EONS, and all of them were symptomatic. Seventy‐eight % (334/426) of the women in the febrile group received epidural analgesia compared to 5% (16/311) in the afebrile group. Of the 95 neonates born to women with chorioamnionitis, one (1.0%) of the neonates born to women with chorioamnionitis developed sepsis.ConclusionsIntrapartum maternal fever is an unreliable predictor for EONS and leads to unnecessary antibiotic treatment. Symptoms in the neonate are a more reliable indicator of an ill neonate with blood culture‐proven sepsis.
Variation in desert shrub foliar pH in relation to drought and salinity in Xinjiang, China
Authors: Luo Yan , Yan Zhengbing , Liu Sining , Chen Jiashu , Li Kaihui , Mohammat Anwar , Han Wenxuan 
Published: April 2021

AbstractAimFoliar pH, an emerging plant functional trait, plays a key role in plant eco‐physiological processes. However, it remains unclear how foliar pH varies among plants with different preferences concerning soil salinity, and how it responds to drought stress in desert ecosystems.LocationXinjiang, northwestern China (40.24° N to 46.24° N, 80.66° E to 91.33° E).MethodsWe addressed variation in foliar pH in four desert shrub groups (i.e., euhalophytes, secretohalophytes, pseudohalophytes and glycophytes) with differing adaptive strategies to soil salinity in 29 sites in Xinjiang, China, and explored the effects of drought and saline stress on foliar pH variability.ResultsWe found that average foliar pH of desert shrubs was 5.54 ± 0.02, higher than that of shrubs from humid areas. At the functional group level, euhalophytes (5.65 ± 0.03) and glycophytes (5.61 ± 0.04) had significantly higher foliar pH than secretohalophytes (5.47 ± 0.03) and pseudohalophytes (5.39 ± 0.05). Coverage‐weighted mean foliar pH of glycophytes‐dominated communities was significantly higher (5.80 ± 0.18) than those of the halophytes‐dominated communities (5.34 ± 0.07 ~ 5.49 ± 0.07). Only in pseudohalophytes there was a significant relationship between foliar pH and both drought stress (i.e., low soil water stress coefficient, aridity index, and mean annual precipitation) and saline stress (shown by high soil electrical conductivity and soil pH). In contrast, secretohalophytes displayed opposite or non‐significant relationships between foliar pH and drought and saline stress. Compared with salinity indicators, drought exerted a much larger impact on foliar pH, particularly in pseudohalophytes and secretohalophytes.ConclusionsOur work documented a comprehensive analysis of foliar pH across halophyte and glycophyte shrub species, and found contrasting responses of foliar pH to drought and salinity in desert ecosystems, which can provide an alternative perspective for understanding the survival strategies of desert plants, and may also offer new insights into the population dynamics of desert shrub communities under global climate change.