bluuebunny/crossref_metadata_2025_split huggingface dataset:
The counterregulatory response to hypoglycaemia in the pig
Authors: Gradel Anna Katrina J. , Kildegaard Jonas , Ludvigsen Trine P. , Porsgaard Trine , Schou‐Pedersen Anne Marie V. , Fels Johannes J. , Lykkesfeldt Jens , Refsgaard Hanne H. F. 
Published: April 2020

AbstractThe domestic pig is commonly used as animal model in the pharmaceutical development of new therapeutics for treatment of diabetes. Since a formal definition of hypoglycaemia only exists in humans, the purpose of this study was to assess the counterregulatory response in the domestic pig at glucose levels known to induce symptoms of hypoglycaemia in humans. Six pigs were included in hyperinsulinaemic glucose clamps with plasma glucose targets of 2, 3 and 5 mmol/L in a cross‐over design, and the associated glucose counterregulatory response was assessed by measuring glucose kinetics and levels of glucagon, c‐peptide, catecholamines, cortisol and growth hormone. Results showed that the 2 and 3 vs 5 mmol/L clamps significantly decreased and increased the secretion of c‐peptide and glucagon, respectively (P < .05). This finding was associated with increased rate of glucose appearance (Ra) and decreased rate of glucose disappearance (Rd) (P < .001). No marked differences in the catecholamine, growth hormone or cortisol response were observed. Consequently, like humans, pigs respond to hypoglycaemia by decreasing the pancreatic output of insulin while increasing that of glucagon, with increased glucose mobilization and decreased glucose disposal as a result. The hypoglycaemic clamps did not result in a marked secretion of the other counterregulatory hormones.
Epistemic vigilance online: Textual inaccuracy and children's selective trust in webpages
Authors: Einav Shiri , Levey Alexandria , Patel Priya , Westwood Abigail 
Published: April 2020

In this age of ‘fake news’, it is crucial that children are equipped with the skills to identify unreliable information online. Our study is the first to examine whether children are influenced by the presence of inaccuracies contained in webpages when deciding which sources to trust. Forty‐eight 8‐ to 10‐year‐olds viewed three pairs of webpages, relating to the same topics, where one webpage per pair contained three obvious inaccuracies (factual, typographical, or exaggerations, according to condition). The paired webpages offered conflicting claims about two novel facts. We asked participants questions pertaining to the novel facts to assess whether they systematically selected answers from the accurate sources. Selective trust in the accurate webpage was found in the typos condition only. This study highlights the limitations of 8‐ to 10‐year‐olds in critically evaluating the accuracy of webpage content and indicates a potential focus for educational intervention.
Statement of contribution

What is already known on this subject?

Children display early epistemic vigilance towards spoken testimony.

They use speakers’ past accuracy when deciding whom to trust regarding novel information.

Little is known about children’s selective trust towards web‐based sources.

What does this study add?

This study is the first to examine whether textual inaccuracy affects children’s trust in webpages.

Typos but not semantic errors led to reduced trust in a webpage compared to an accurate source.

Children aged 8‐10 years show limited evaluation of the accuracy of online content.
The joint effect of genetic risk factors and different types of combined oral contraceptives on venous thrombosis risk
Authors: Khialani Deeksha , le Cessie Saskia , Lijfering Willem M. , Cannegieter Suzanne C. , Rosendaal Frits R. , van Hylckama Vlieg Astrid 
Published: April 2020

AbstractIt is not known whether the synergistic effect of genetic markers, increasing the risk of venous thrombosis (VT), and combined oral contraceptives (COC) use varies between different types of progestogens in these preparations. We investigated the joint effect of genetic risk factor, that is, F5 rs6025, F2 rs1799963, and FGG rs2066865 mutations, and different progestogens on the risk of VT. The constrained maximum likelihood estimation (CMLE) method was used to calculate joint effects, expressed as odds ratio (OR) with 95% confidence intervals [CI]. As the dose of estrogen is known to be a risk factor for VT, analyses were restricted to COC with 30 µg estrogen and each progestogen. Overall, the joint effect of COC and genetic variants was lowest for COC containing the progestogen levonorgestrel, albeit CIs were wide. The OR (95% CI) of the four different analyses (i.e. joint effect with F5 rs6025, F2 rs1799963, F5 rs6025 or F2 rs1799963 and FGG rs2066865) ranged between 7·4 (5·4–10·2) and 24·8 (12·3–50·0) for levonorgestrel. For gestodene the joint effect ranged between 11·7 (7·2–19·1) and 30·9 (10·6–89·9). Desogestrel and cyproterone acetate had the highest risk estimates: 14·6 (9·7–21·9) and 32·6 (13·2–80·6) and 15·5 (9·7–24·9) and 44·4 (16·9–116·3) respectively. In women with inherited thrombophilia, COC containing levonorgestrel were associated with the lowest risk of VT, albeit the CIs were wide.
Effects of spatial autocorrelation and sampling design on estimates of protected area effectiveness
Authors: Negret Pablo Jose , Marco Moreno Di , Sonter Laura J. , Rhodes Jonathan , Possingham Hugh P. , Maron Martine 
Published: April 2020

AbstractEstimating the effectiveness of protected areas (PAs) in reducing deforestation is useful to support decisions on whether to invest in better management of areas already protected or to create new ones. Statistical matching is commonly used to assess this effectiveness, but spatial autocorrelation and regional differences in protection effectiveness are frequently overlooked. Using Colombia as a case study, we employed statistical matching to account for confounding factors in park location and accounted for for spatial autocorrelation to determine statistical significance. We compared the performance of different matching procedures—ways of generating matching pairs at different scales—in estimating PA effectiveness. Differences in matching procedures affected covariate similarity between matched pairs (balance) and estimates of PA effectiveness in reducing deforestation. Independent matching yielded the greatest balance. On average 95% of variables in each region were balanced with independent matching, whereas 33% of variables were balanced when using the method that performed worst. The best estimates suggested that average deforestation inside protected areas in Colombia was 40% lower than in matched sites. Protection significantly reduced deforestation, but PA effectiveness differed among regions. Protected areas in Caribe were the most effective, whereas those in Orinoco and Pacific were least effective. Our results demonstrate that accounting for spatial autocorrelation and using independent matching for each subset of data is needed to infer the effectiveness of protection in reducing deforestation. Not accounting for spatial autocorrelation can distort the assessment of protection effectiveness, increasing type I and II errors and inflating effect size. Our method allowed improved estimates of protection effectiveness across scales and under different conditions and can be applied to other regions to effectively assess PA performance.
Gene regulatory landscape of the sonic hedgehog locus in embryonic development
Authors: Amano Takanori 
Published: April 2020

AbstractThe organs of vertebrate species display a wide variety of morphology. A remaining challenge in evolutionary developmental biology is to elucidate how vertebrate lineages acquire distinct morphological features. Developmental programs are driven by spatiotemporal regulation of gene expression controlled by hundreds of thousands of cis‐regulatory elements. Changes in the regulatory elements caused by the introduction of genetic variants can confer regulatory innovation that may underlie morphological novelties. Recent advances in sequencing technology have revealed a number of potential regulatory variants that can alter gene expression patterns. However, a limited number of studies demonstrate causal dependence between genetic and morphological changes. Regulation of Shh expression is a good model to understand how multiple regulatory elements organize tissue‐specific gene expression patterns. This model also provides insights into how evolution of molecular traits, such as gene regulatory networks, lead to phenotypic novelty.
Child mental health literacy training programmes for professionals in contact with children: A systematic review
Authors: O'Connell Jennifer , Pote Helen , Shafran Roz 
Published: April 2020

AbstractAimsThere has been a surge in child mental health literacy training programmes for non‐mental health professionals. No previous review has examined the effectiveness of child mental literacy training on all professionals in contact with children.MethodsStudies were identified through a systematic literature search of the Cochrane, EMBASE, Medline, and PsycINFO databases in February 2019. The review included studies that delivered training to professionals who have regular contact with young people aged 0 to 19 in the context of their role and at least one component of mental health literacy; (a) knowledge, (b) attitudes, (c) confidence in helping, (d) intention to help and (e) actual helping behaviour. The quality of papers was reviewed using the Cochrane revised Risk of Bias Tool for randomized controlled trials (RCTs) and the Integrated Quality Criteria for the Review of Multiple Study Designs for non RCTs.ResultsTwenty‐one studies met eligibility criteria (n = 3243). There was some evidence that global and specific child mental health literacy training improved professionals' knowledge and stigma‐related attitudes towards mental health. Few studies investigated the impact of training on actual helping behaviour.ConclusionThere may be value in providing child mental health literacy training to professionals in contact with children, however there is a need for studies to evaluate the long‐term impact of such training, particularly on subsequent access to appropriate support. Findings raise concerns about the quality of the studies reported in the systematic review and recommendations are made for future studies.
Functional implications of CaMKII alternative splicing
Authors: Sloutsky Roman , Stratton Margaret M. 
Published: April 2020

AbstractCa2+/calmodulin‐dependent protein kinase II (CaMKII) is known to be a crucial regulator in the post‐synapse during long‐term potentiation. This important protein has been the subject of many studies centered on understanding memory at the molecular, cellular, and organismic level. CaMKII is encoded by four genes in humans, all of which undergo alternative splicing at the RNA level, leading to an enormous diversity of expressed proteins. Advances in sequencing technologies have facilitated the discovery of many new CaMKII transcripts. To date, newly discovered CaMKII transcripts have been incorporated into an ambiguous naming scheme. Herein, we review the initial experiments leading to the discovery of CaMKII and its subsequent variants. We propose the adoption of a new, unambiguous naming scheme for CaMKII variants. Finally, we discuss biological implications for CaMKII splice variants.
Sherlock Holmes and the Case of Resist/Refuse Dynamics: Confirmatory Bias and Abductive Inference in Child Custody Evaluations
Authors: Garber Benjamin D. 
Published: April 2020

Had Sir Arthur Conan Doyle's fictional detective, the great Sherlock Holmes, actually engaged in deductive reasoning, he would have solved many fewer crimes. In fact, Holmes' logical progression from astute observation to hypotheses is a model of a type of inductive reasoning. This paper argues that mental health professionals tasked to evaluate why a child is resisting/refusing contact with one parent must approach each family the way that Holmes approached each case, without a presumed suspect, moving systematically from detail to hypothesis, well‐versed in the full range of dynamics that may be at play, and erring in favor of parsimony rather than pathology. By contrast, the custody evaluator who approaches these matters through a deductive process, seeking data that support an a priori theory, is vulnerable to confirmatory bias and doing harm to the child whose interests are paramount. The literature concerned with resist/refuse dynamics is reviewed, yielding 13 non‐mutually exclusive variables that evaluators must consider so as to more fully identify why a particular child is resisting or refusing contact with one parent. On this basis, the hybrid model is expanded to include the full spectrum of contributing dynamics. Specific recommendations are made for judicial officers in the interest of writing orders for custody evaluations that minimize the risk of confirmatory bias.Key Points for the Family Court Community
Deductive reasoning seeks to confirm or refute an a priori hypothesis
Deductive reasoning is highly vulnerable to confirmational bias
Confirmational bias can corrupt and invalidate forensic evaluation to the detriment of all involved
Resist/refuse dynamics must be understood through an inductive process that is open to all possible hypotheses
A survey of the literature identifies at least thirteen mutually compatible hypotheses, all of which must be evaluated
Courts must take care to word orders for forensic family evaluations in a manner that minimizes confirmatory bias and invites inductive investigation
Robust ecological drought projections for drylands in the 21st century
Authors: Bradford John B. , Schlaepfer Daniel R. , Lauenroth William K. , Palmquist Kyle A. 
Published: April 2020

AbstractDryland ecosystems may be especially vulnerable to expected 21st century increases in temperature and aridity because they are tightly controlled by moisture availability. However, climate impact assessments in drylands are difficult because ecological dynamics are dictated by drought conditions that are difficult to define and complex to estimate from climate conditions alone. In addition, precipitation projections vary substantially among climate models, enhancing variation in overall trajectories for aridity. Here, we constrain this uncertainty by utilizing an ecosystem water balance model to quantify drought conditions with recognized ecological importance, and by identifying changes in ecological drought conditions that are robust among climate models, defined here as when >90% of models agree in the direction of change. Despite limited evidence for robust changes in precipitation, changes in ecological drought are robust over large portions of drylands in the United States and Canada. Our results suggest strong regional differences in long‐term drought trajectories, epitomized by chronic drought increases in southern areas, notably the Upper Gila Mountains and South‐Central Semi‐arid Prairies, and decreases in the north, particularly portions of the Temperate and West‐Central Semi‐arid Prairies. However, we also found that exposure to hot‐dry stress is increasing faster than mean annual temperature over most of these drylands, and those increases are greatest in northern areas. Robust shifts in seasonal drought are most apparent during the cool season; when soil water availability is projected to increase in northern regions and decrease in southern regions. The implications of these robust drought trajectories for ecosystems will vary geographically, and these results provide useful insights about the impact of climate change on these dryland ecosystems. More broadly, this approach of identifying robust changes in ecological drought may be useful for other assessments of climate impacts in drylands and provide a more rigorous foundation for making long‐term strategic resource management decisions.
Community pharmacy staff oral health training, training needs and professional self-efficacy related to managing children’s dental problems
Authors: Muirhead Vanessa , D’Antoni Donatella , Auyeung Vivian 
Published: April 2020

Abstract

Objectives
Few studies have explored the oral health training needs and professional self-efficacy (PSE) in both pharmacy support staff and pharmacists related to managing children’s dental problems. This study assessed community pharmacy staff perceptions of their (i) training experiences and interests; (ii) PSE; and (iii) whether this was influenced by the pharmacy being part of a minor ailment scheme (MAS), where staff could directly offer advice and issue prescription medications without patients seeing a doctor.

Methods
All of the 1851 community pharmacies across London, UK, were invited to participate in an online questionnaire. Staff rated their prior training, perceived need for further training and confidence in giving parents advice related to three dental problems in children (dental pain, mouth ulcers and dental trauma). Information was collected about staff roles and whether the pharmacy was a MAS.

Key findings
From 752 community pharmacies, 846 community pharmacy staff participated. Positive experiences of training were variable but interest in further training for all three dental problems was high. Pharmacy support staff had significantly lower PSE scores than pharmacy professionals (P = 0.009). A significant interaction showed that pharmacy staff who had poorly rated prior training on advising parents about managing their child’s dental pain and who did not work in a MAS had lower PSE scores than staff who had highly rated training and who worked in a MAS (P = 0.02).

Conclusions
Minor ailment scheme pharmacies may be an optimal environment for frontline pharmacy support staff to develop higher PSE when combined with good quality oral health training.
More than coffee – a World Café to explore enablers of pharmacy practice research
Authors: Kavanagh Oisín N , Moriarty Frank , Bradley Catriona , O’Hagan James , Stack Gary , Kelly Dervla 
Published: April 2020

Abstract

Background
Pharmacists are in demand now more than ever to provide high-quality expertise about the effectiveness, safety and use of medications. Amidst an increasingly complex and costly healthcare system, policy makers need robust evidence to justify public spending on pharmacy services. Research on the impact of existing and emerging pharmacy practices is required.

Objective
To explore barriers and opportunities to enhance research among pharmacists in Ireland utilising a World Café methodology.

Methods
A pharmacy research discussion day was held in November 2018, open to all pharmacists in Ireland. A World Café methodology was utilised as a mechanism to facilitate group discussions about pharmacy practice research.

Results
Discussions with 63 attendees identified four themes and seventeen subthemes. The four themes were challenges undertaking research, research motivations, leadership and training. Subthemes included robust evidence, clinical, economic and societal outcomes, alignment with national and international health system priorities, need for incentives from professional training bodies, competitive business model and embed within schools of pharmacy.

Conclusions
The most commonly discussed barriers inhibiting research were workload, technology limitations and financial considerations. Organisational leadership to prioritise and coordinate research efforts, training to build research capacity, building on existing examples of excellence and initiation of bottom-up community-based research projects were identified in our study as opportunities to enhance pharmacist involvement in research and ultimately patient health outcomes.
Achieving stable myocardial regeneration after apical resection in neonatal mice
Authors: Li Yandong , Feng Jie , Li Yan , Hu Shengshou , Nie Yu 
Published: April 2020

AbstractThe neonatal heart completely regenerates after apical resection (AR), providing a desirable research model to study the mechanism of cardiac regeneration and cardiomyocyte proliferation. However, AR‐induced neonatal heart regenerative phenomenon is controversial due to the variation of operative details in different laboratories. Here, we provide an optimized AR operation procedure with stable regeneration and high survival rate by achieving heart exposure, normalizing myocardium cut‐offs, and reducing operation duration. We also established a whole‐heart‐slice approach to estimate the myocardial regeneration after the AR operation, which ensures no false‐negative/positive results. The combination of the optimized AR operation and the whole‐heart‐slice analysis provides a stable system to study neonatal heart regeneration and cardiomyocyte proliferation in situ.
Rules of thumb for positive and negative test results
Authors: Šikić Zvonimir 
Published: April 2020

AbstractBackgroundIt is well known that tests are not 100% accurate at classifying individuals. The actual condition of an individual(e.g. diseased, or not diseased) does not coincide with her test result (positive, or negative). Nevertheless, it is often presupposed, as a rule of thumb, that individuals with negative results can be “ruled out” if screening test is highly sensitive and “ruled in” if screening test is highly specific. This has led to the mnemonic SNNOUT (sensitive negative out) and SPPIN (specific positive in).MethodProbabilistic analysis of SNNOUT and SPPIN.ResultSNNOUT and SPPIN are incorrect. We devise the correct and easily applicable rules of thumb.ConclusionThe correct rules of thumb could be of great help to doctors and patients.
SmMYB2 promotes salvianolic acid biosynthesis in the medicinal herb Salvia miltiorrhiza
Authors: Deng Changping , Wang Yao , Huang Fenfen , Lu Sunjie , Zhao Limei , Ma Xingyuan , Kai Guoyin 
Published: April 2020

AbstractMYB transcription factors play vital roles in plant growth and metabolism. The phytohormone methyl jasmonate (MeJA) promotes phenolic acid accumulation in the medicinal herb Salvia miltiorrhiza, but the regulatory mechanism is poorly understood. Here, we identified the MeJA‐responsive R2R3‐MYB transcription factor gene SmMYB2 from a transcriptome library produced from MeJA‐treated S. miltiorrhiza hairy roots. SmMYB2 expression was tightly correlated with the expression of key salvianolic acid biosynthetic genes including CYP98A14. SmMYB2 was highly expressed in the periderm of S. miltiorrhiza and SmMYB2 localized to the nucleus. Overexpressing SmMYB2 in S. miltiorrhiza hairy roots significantly increased the levels of salvianolic acids (including rosmarinic acid and salvianolic acid B) by upregulating salvianolic acid biosynthetic genes such as CYP98A14. SmMYB2 binds to the MYB‐binding motifs in the promoter of CYP98A14, as confirmed by a dual‐luciferase assay and electrophoretic mobility shift assays. Anthocyanin contents were significantly higher in SmMYB2‐overexpressing hairy root lines than the control, primarily due to the increased expression of CHI, DFR, and ANS. These findings reveal the novel regulatory role of SmMYB2 in MeJA‐mediated phenolic acid biosynthesis, providing a useful target gene for metabolic engineering and shedding light on the salvianolic acid regulatory network.