bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of a targeted monitoring on data‐quality and data‐management workload of randomized controlled trials: A prospective comparative study
Authors: Fougerou‐Leurent Claire , Laviolle Bruno , Tual Christelle , Visseiche Valérie , Veislinger Aurélie , Danjou Hélène , Martin Amélie , Turmel Valérie , Renault Alain , Bellissant Eric 
Published: August 2019

AimsMonitoring risk‐based approaches in clinical trials are encouraged by regulatory guidance. However, the impact of a targeted source data verification (SDV) on data‐management (DM) workload and on final data quality needs to be addressed.MethodsMONITORING was a prospective study aiming at comparing full SDV (100% of data verified for all patients) and targeted SDV (only key data verified for all patients) followed by the same DM program (detecting missing data and checking consistency) on final data quality, global workload and staffing costs.ResultsIn all, 137 008 data including 18 124 key data were collected for 126 patients from 6 clinical trials. Compared to the final database obtained using the full SDV monitoring process, the final database obtained using the targeted SDV monitoring process had a residual error rate of 1.47% (95% confidence interval, 1.41–1.53%) on overall data and 0.78% (95% confidence interval, 0.65–0.91%) on key data. There were nearly 4 times more queries per study with targeted SDV than with full SDV (mean ± standard deviation: 132 ± 101 vs 34 ± 26; P = .03). For a handling time of 15 minutes per query, the global workload of the targeted SDV monitoring strategy remained below that of the full SDV monitoring strategy. From 25 minutes per query it was above, increasing progressively to represent a 50% increase for 45 minutes per query.ConclusionTargeted SDV monitoring is accompanied by increased workload for DM, which allows to obtain a small proportion of remaining errors on key data (<1%), but may substantially increase trial costs.
Clinoforms as paleogeographic tools: Development of the Danube catchment above the deep Paratethyan basins in Central and Southeast Europe
Authors: Magyar Imre , Krezsek Csaba , Tari Gabor 
Published: August 2019

AbstractThe Miocene marine basins of Central and Southeast Europe, once comprising the Paratethys Sea, were gradually filled with sediments during the Neogene and turned to be the catchment area of the proto‐Danube and finally that of the modern Danube. Seismic data from various parts of the large Danube catchment area show that these several hundred meter deep basins were filled by lateral accretion of river‐transported sediments, appearing as shelf edge scale clinoform sets in seismic profiles. The direction of shelf edge progradation is NW to SE (N to S, W to E) in each basin, except for the Dacian basin where NE to SW direction prevails. The age of the clinoform sets is generally younging downstream: 19–18 Ma in the North Alpine Foreland basin, 14–13 Ma in the Vienna basin, 10–9 Ma in the Danube (Kisalföld) basin, 8.6–4 Ma in the Central Pannonian basin (Alföld), ?9–5 Ma in the Dacian basin, and 6–0 Ma in the Euxinian (Black Sea) basin. In spite of this geographical and temporal pattern, only the Danube (Kisalföld) and the western and central part of the Central Pannonian basin were filled by the proto‐Danube shelf accretion. Formation of the Danube, as a longitudinal river of the Alpine foreland that gradually elongated to the east and followed the retreating shoreline of the Paratethys, most probably took place at the beginning of the Late Miocene, ca. 11 Ma ago, thus the Early and Middle Miocene shelf advance in the North Alpine Foreland and Vienna basins, respectively, cannot be attributed to a „paleo‐Danube”. The clinoform systems of the Dacian basin are coeval with those of the upstream Central Pannonian basin, indicating that by the time the Danube sedimentary system reached the Dacian basin, it was already a shallow basin. The vast clinoforms of the northwestern Euxinian shelf also significantly overlap in age with the Pannonian basin ones; only the <4 Ma part of the shelf accretion can be attributed to the Danube sensu stricto.
Minibasin depocentre migration during diachronous salt welding, offshore Angola
Authors: Ge Zhiyuan , Gawthorpe Rob L. , Rotevatn Atle , Zijerveld Leo , A.‐L. Jackson Christopher , Oluboyo Ayodeji 
Published: August 2019

AbstractSalt tectonics is an important part of the geological evolution of many continental margins, yet the four‐dimensional evolution of the minibasins, the fundamental building block of these and many other salt basins, remains poorly understood. Using high‐quality 3D seismic data from the Lower Congo Basin, offshore Angola we document the long‐term (>70 Myr) dynamics of minibasin subsidence. We show that, during the Albian, a broadly tabular layer of carbonate was deposited prior to substantial salt flow, diapirism, and minibasin formation. We identify four subsequent stages of salt‐tectonics and related minibasin evolution: (i) thin‐skinned extension (Cenomanian to Coniacian) driven by basinward tilting of the salt layer, resulting in the formation of low‐displacement normal faults and related salt rollers. During this stage, local salt welding led to the along‐strike migration of fault‐bound depocentres; (ii) salt welding below the eastern part of the minibasin (Santonian to Paleocene), causing a westward shift in depocentre location; (iii) welding below the minibasin centre (Eocene to Oligocene), resulting in the formation of a turtle and an abrupt shift of depocentres towards the flanks of the bounding salt walls; and (iv) an eastward shift in depocentre location due to regional tilting, contraction, and diapir squeezing (Miocene to Holocene). Our study shows that salt welding and subsequent contraction are key controls on minibasin geometry, subsidence and stratigraphic patterns. In particular, we show how salt welding is a protracted process, spanning > 70 Myr of the salt‐tectonic history of this, and likely other salt‐rich basins. The progressive migration of minibasin depocentres, and the associated stratigraphic architecture, record weld dynamics. Our study has implications for the tectono‐stratigraphic evolution of minibasins.
Comparative assessment of anterior maxillary alveolar ridge preservation with and without adjunctive use of enamel matrix derivative: A randomized clinical trial
Authors: Lee Jae‐Hong , Kim Do‐Hyung , Jeong Seong‐Nyum 
Published: August 2019

AbstractObjectivesThe aim of this randomized, controlled, parallel‐arm study was to evaluate the (a) radiographic bone dimensional changes, (b) postoperative discomfort, and (c) early soft tissue wound healing outcomes, following extraction of maxillary anterior teeth (central and lateral incisors) and treatment with alveolar ridge preservation (ARP) with and without the adjunctive use of enamel matrix derivative (EMD).MethodsThirty extraction sockets were randomly assigned to two groups: deproteinized bovine bone mineral with 10% collagen covered with collagen membrane with the adjunctive use of EMD (test group) and without EMD (control group). Bone dimensional changes were measured using cone beam computed tomography at 3 and 5 months after ARP. The severity and duration of pain and swelling were evaluated using self‐reported questionnaires, and soft tissue wound healing outcomes were assessed clinically. Chi‐square tests and t tests were conducted to compare differences between the two groups.ResultsRadiographic and clinical analyses showed no significant differences in horizontal and vertical bone dimensional changes and soft tissue wound healing outcomes (including spontaneous bleeding, persistent swelling, and ulceration) between the two groups. There were no significant differences in the severity of pain and swelling between the two groups, but the durations of pain (difference [df] = 1.20, 95% CI = 0.33–2.06; p = .008) and swelling (df = 1.06, 95% CI = 0.11–2.01; p = .029) were significantly reduced in the test group.ConclusionAlveolar ridge preservation with the adjunctive use of EMD reduced the durations of postoperative pain and swelling following maxillary anterior teeth extraction.
Metabolomics analysis reveals perturbations of cerebrocortical metabolic pathways in the Pahenu2 mouse model of phenylketonuria
Authors: Lu Li‐Hua , Xia Zheng‐Xiang , Guo Jia‐Lin , Xiao Ling‐Ling , Zhang Yong‐Jun 
Published: August 2019

AbstractAimsPhenylketonuria (PKU), which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, is one of the most common inherited diseases of amino acid metabolism. Phenylketonuria is characterized by an abnormal accumulation of phenylalanine and its metabolites in body fluids and brain tissues, subsequently leading to severe brain dysfunction. Various pathophysiological and molecular mechanisms underlying brain dysfunction in PKU have been described. However, the metabolic changes and their impacts on the function of cerebral cortices of patients with PKU remain largely unknown.MethodsWe measured the levels of small molecule metabolites in the cerebrocortical tissues of PKU mice and wild‐type control mice using liquid chromatography‐mass spectrometry (LC‐MS)‐based metabolome analysis. Differential metabolites were further subjected to metabolic pathway and enrichment analysis.ResultsMetabolome analysis revealed 35 compounds among 143 detected metabolites were significantly changed in PKU mice as compared to those in their wild‐type littermates. Metabolic pathway and enrichment analysis of these differential metabolites showed that multiple metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine biosynthesis; alanine, aspartate, and glutamate metabolism; purine metabolism; arginine and proline metabolism and methionine metabolism, were impacted in the cerebral cortices of PKU mice.ConclusionsThe data revealed that multiple metabolic pathways in cerebral cortices of PKU mice were disturbed, suggesting that the disturbances of the metabolic pathways might contribute to neurological or neurodevelopmental dysfunction in PKU, which could thus provide new insights into brain pathogenic mechanisms in PKU as well as mechanistic insights for better understanding the complexity of the metabolic mechanisms of the brain dysfunction in PKU.
Evaluation of subvalvular pannus formation in mechanical aortic valve by transesophageal echocardiography
Authors: Karaduman Ahmet , Balaban İsmail , Keskin Berhan , Kalkan Semih , Keten Mustafa Ferhat , Kafkas Çağrı , Ayturk Mehmet , Kahveci Gökhan 
Published: August 2019

AbstractSubvalvular pannus formation is a rare but clinically important complication with prosthetic valves. Transthoracic echocardiography still plays a role in the initial assessment of mechanical aortic valve dysfunction. But evaluation with transesophageal echocardiography is more useful. Subvalvular area may be a blind spot of echocardiography due to acoustic shadowing. The case presented herein underlines the significant role of transgastric plane and three‐dimensional TEE in the assessment of subvalvular pannus formation in mechanical aortic valves.
Right aortic arch with mirror image branching accompanied by absent pulmonary valve syndrome and tricuspid stenosis: Prenatal echocardiographic diagnosis of an unusual congenital heart defect
Authors: Yang Zexuan , Zhou Liuying 
Published: August 2019

AbstractRight aortic arch (RAA) with mirror image branching (RAMI) accompanied by absent pulmonary valve syndrome (APVS), tricuspid stenosis, and hypoplastic right ventricle is an extremely rare combination of congenital heart anomalies. This combination might result in severe cardiac failure and respiratory compromise, indicating a poor prognosis. Here, we describe a detailed prenatal echocardiographic diagnosis of RAMI accompanied by APVS and tricuspid stenosis. These anomalies were further confirmed by autopsy. This case could be helpful in improving our understanding of this abnormal combination and the development of an early therapeutic strategy.
Immediate post‐operative rehabilitation after decoronation. A systematic review
Authors: Einy Shmuel , Kridin Khalaf , Kaufman Arieh Y. , Cohenca Nestor 
Published: August 2019

AbstractBackground/AimsDecoronation is currently considered the best treatment option for ankylosed teeth and discrepancies in the alveolar bone, particularly in childhood and adolescence. The loss of a front tooth creates aesthetic, functional, and psychological distress in patients and their parents. The aim of this study was to analyze the types of restorations provided after decoronation, their suitability, durability, and follow up until insertion of the final restoration.Materials and methodsA literature review was conducted using Ovid MEDLINE, Embase, and Web of Science to identify eligible articles. English language publications until August 9, 2018, were searched independently and cross‐checked by two researchers online, in print, and in press.ResultsOf 618 articles screened, 10 included reports on 11 patients with detailed descriptions of 13 provisional restorations. Patients' ages at the time of decoronation were 8‐15 years. Seven underwent avulsion and four intrusion. Removable partial denture (nine cases) was the most common restoration. In two cases, the restoration was provisional with a lingual bar with prosthetic crown and in two other cases with an adhesive bridge. Follow up ranged from 3 months to 5 years in nine patients. Two cases were followed until the permanent restoration was placed.ConclusionsThe importance of long‐term provisional restorations was disregarded by most authors. A multidisciplinary approach should take into consideration immediate‐, mid‐, and long‐term rehabilitation of the decoronated tooth.
Single housing‐induced effects on cognitive impairment and depression‐like behavior in male and female mice involve neuroplasticity‐related signaling
Authors: Liu Na , Wang Yulu , An Aerin Y. , Banker Christopher , Qian Yi‐Hua , O'Donnell James M. 
Published: August 2019

AbstractSingle‐housed stress elicits a range of social isolation‐related behavioral and neurobiological abnormalities. To investigate single housing‐induced behavioral changes and sex differences on stress outcomes, we examined single‐housed stress‐induced learning and memory impairment, depression‐like behaviors, neuroplasticity abnormalities and underlying mechanism. The results showed that male and female mice socially isolated for 8 weeks had significantly decreased memory acquisition, as demonstrated in the learning curve of the Morris water maze task. Memory consolidation and retrieval were also decreased in both the single‐housed male and female mice. These findings were corroborated further by the two classical animal models, Y‐maze and novel object recognition tests, as demonstrated by reduced spontaneous alternation and recognition index in both sexes of single‐housed mice. Subsequent studies suggested that single‐housed male mice exhibited increased immobility time in both the forced swim and tail suspension tests, while the female mice only exhibited increased immobility time in the tail suspension test. Moreover, single‐housed stress significantly decreased the apical and basal branch points, dendritic length, and spine density in the CA1 of hippocampal neurons in both male and female mice. These effects were consistent with decreased neuroplasticity and neuroprotective‐related molecules such as synaptophysin, PSD95, PKA, pCREB and BDNF expression. These findings suggest that loss of neuronal remodeling and neuroprotective mechanisms due to single housing are involved in behavioral changes in both male and female mice. The results provide further evidence that neuroplasticity‐related signaling plays a crucial role in isolation‐induced effects on neuropsychiatric behavioral deficits in both sexes.
When can we trust responders? Serious concerns when using 50% response rate to assess clinical trials
Authors: Karoly Philippa J. , Romero Juan , Cook Mark J. , Freestone Dean R. , Goldenholz Daniel M. 
Published: August 2019

AbstractIndividual seizure rates are highly volatile, with large fluctuations from month‐to‐month. Nevertheless, changes in individual mean seizure rates are used to measure whether or not trial participants successfully respond to treatment. This study aims to quantify the challenges in identifying individual treatment responders in epilepsy. A power calculation was performed to determine the trial duration required to detect a significant 50% decrease in seizure rates (P < .05) for individuals. Seizure rate simulations were also performed to determine the number of people who would appear to be 50% responders by chance. Seizure rate statistics were derived from long‐term seizure counts recorded during a previous clinical trial for an implantable seizure monitoring device. We showed that individual variance in monthly seizure rates can lead to an unacceptably high false‐positive rate in the detection of individual treatment responders. This error rate cannot be reduced by increasing the trial population; however, it can be reduced by increasing the duration of clinical trials. This finding suggests that some drugs may be incorrectly evaluated as effective; or, conversely, that helpful drugs could be rejected based on 50% response rates. It is important to pursue more nuanced approaches to measuring individual treatment response, which consider the patient‐specific distributions of seizure rates.
A novel taxon selection method, aimed at minimizing recombination, clarifies the discovery of a new sub‐population of Helicobacter pylori from Australia
Authors: Lamichhane Binit , Wise Michael J. , Chua Eng Guan , Marshall Barry J. , Tay Chin Yen 
Published: August 2019

AbstractWe present a novel method for taxon selection, the aim being to minimize problems arising from highly recombinant species such as Helicobacter pylori. Helicobacter pylori has accompanied modern‐human migration out of Africa and is marked by a phylogeographic strain distribution, which has been exploited to add an extra layer of information about human migrations to that obtained from human sources. However, H. pylori's genome has high sequence heterogeneity combined with a very high rate of recombination, causing major allelic diversification across strains. On the other hand, recombination events that have become preserved in sub‐populations are a useful source of phylogenetic information. This creates a potential problem in selecting representative strains for particular genetic or phylogeographic clusters and generally ameliorating the impact on analyses of extensive low‐level recombination. To address this issue, we perform multiple population structure‐based analyses on core genomes to select exemplar strains, called ‘quintessents’, which exhibit limited recombination. In essence, quintessent strains are representative of their specific phylogenetic clades and can be used to refine the current MLST concatenation‐based population structure classification system. The use of quintessents reduces the noise due to local recombination events, while preserving recombination events that have become fixed in sub‐populations. We illustrate the method with an analysis of core genome concatenations from 185 H. pylori strains, which reveals a recent speciation event resulting from the recombination of strains from phylogeographic clade hpSahul, carried by Aboriginal Australians, and hpEurope, carried by some of the people who arrived in Australia over the past 200 years. The signal is much clearer when based on quintessent strains, but absent from the analysis based on MLST concatenations.
Real‐time telehealth using ultrasonography is feasible in equine practice
Authors: Navas de Solis C. , Bevevino K. , Doering A. , O'Gan D. , Teller L. , Underwood C. 
Published: August 2019

SummaryTelehealth allows health care professionals to evaluate patients in remote locations using telecommunications technology. This manuscript presents a pilot experience with the goal of testing the feasibility and exploring the benefits for patients and veterinarians, technological challenges and perceived value of telehealth in ultrasound. In phase 1, experienced equine private practitioners and a sonographer performed diagnostic ultrasound examinations in collaboration using telecommunications technology. In phase 2, horses underwent two consecutive ultrasound examinations. One examination was performed by an inexperienced sonographer assisted by a remote expert, and all horses were then scanned by an expert sonographer on‐site. Information about each interaction was collected, and a questionnaire was used at the end of the project to summarise practitioners’ and trainees’ experiences and perceptions. Thirty‐six cases were evaluated using telecommunications technology. There were technological problems that were minor in 11 occasions, and in one case, the remote assistance had to be cancelled. Sonograms were longer when performed by an inexperienced sonographer aided remotely (40 ± 19, [9–73] min) than when performed by a sonographer (24 ± 12, [4–43 min], P = 0.02). Telehealth for ultrasound was feasible, and technological challenges could be solved. Telehealth for ultrasound was well received by private practitioners, house officers and sonography experts. The perceived benefits were the addition of clinically useful information, reassurance to practitioners and horse owners and education for practitioners. The results of this study support generating the hypothesis that telehealth could in the future increase the quality of equine medicine, and prospective studies are needed to confirm this. Rigorous care will be needed to ensure that implementation of telehealth technology prioritises equine health and the veterinary profession.