bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Clinical Study with AP30663 ‐ a KCa2 Channel Inhibitor in Development for Conversion of Atrial Fibrillation
Authors: Gal Pim , Klaassen Erica S. , Bergmann Kirsten R. , Saghari Mahdi , Burggraaf Jacobus , Kemme Michiel J. B. , Sylvest Christina , Sørensen Ulrik , Bentzen Bo H. , Grunnet Morten , Diness Jonas G. , Edvardsson Nils 
Published: July 2020

Pharmacological cardioversion of atrial fibrillation (AF) is frequently inefficacious. AP30663, a small conductance Ca2+ activated K+ (KCa2) channel blocker, prolonged the atrial effective refractory period in preclinical studies and subsequently converted AF into normal sinus rhythm. This first‐in‐human study evaluated the safety and tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) effects were explored. Forty‐seven healthy male volunteers (23.7 ± 3.0 years) received AP30663 intravenously in ascending doses. Due to infusion site reactions, changes to the formulation and administration were implemented in the latter 24 volunteers. Extractions from a 24‐hour continuous electrocardiogram were used to evaluate the PD effect of AP30663. Data were analyzed with a repeated measure analysis of covariance, noncompartmental analysis, and concentration‐effect analysis. In total, 33 of 34 adverse events considered related to AP30663 exposure were related to the infusion site, mild in severity, and temporary in nature, although full recovery took up to 110 days. After formulation and administration changes, the local infusion site reaction remained, but the median duration was shorter despite higher dose levels. AP30663 displayed a less than dose proportional increase in peak plasma concentration (Cmax) and a terminal half‐life of around 5 hours. In healthy volunteers, no effect of AP30663 was observed on electrocardiographic parameters, other than a concentration‐dependent effect on the corrected QT Fridericia’s formula interval (+18.8 ± 4.3 ms for the highest dose level compared with time matched placebo). In conclusion, administration of AP30663, a novel KCa2 channel inhibitor, was safe and well‐tolerated systemically in humans, supporting further development in patients with AF undergoing cardioversion.
Heart rate variability in patients with atrial fibrillation and hypertension
Authors: Khan Ahsan A. , Junejo Rehan T. , Thomas Graham N. , Fisher James P. , Lip Gregory Y. H. 
Published: July 2020

AbstractBackgroundAtrial fibrillation (AF) and hypertension are independently associated with impaired autonomic function determined using heart rate variability (HRV). As these conditions frequently co‐exist, we sought to determine whether AF would worsen HRV in hypertensive patients.DesignWe studied HRV in AF (and hypertension) (n = 61) and hypertension control group (n = 33). The AF (and hypertension) group was subdivided into permanent AF (n = 30) and paroxysmal AF (n = 31) and re‐studied. Time‐domain, frequency‐domain and nonlinear measures of HRV were determined. Permanent AF group (n = 30) was followed up after 8 weeks following optimisation of their heart rate and blood pressure (BP).ResultsTime‐domain and nonlinear indices of HRV were higher in AF (and hypertension) group compared to hypertensive controls (P ≤ .01). Time‐domain and nonlinear indices of HRV were higher in permanent AF group compared to paroxysmal AF (P ≤ .001). Permanent AF was an independent predictor of HRV on multivariable analysis (P = .006). Optimisation of heart rate and BP had no significant impact on HRV in permanent AF.ConclusionsAF, independent of hypertension, is characterised with marked HRV and is possibly related to vagal tone. HRV is higher in permanent AF compared to paroxysmal AF suggesting evident autonomic influence in the pathophysiology of permanent AF. Modulation of autonomic influence on cardiovascular system should be explored in future studies.
Predictors of adverse prognosis in COVID‐19: A systematic review and meta‐analysis
Authors: Figliozzi Stefano , Masci Pier Giorgio , Ahmadi Navid , Tondi Lara , Koutli Evangelia , Aimo Alberto , Stamatelopoulos Kimon , Dimopoulos Meletios‐Athanasios , Caforio Alida L. P. , Georgiopoulos Georgios 
Published: July 2020

AbstractBackgroundIdentification of reliable outcome predictors in coronavirus disease 2019 (COVID‐19) is of paramount importance for improving patient's management.MethodsA systematic review of literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in‐hospital mortality. We extracted numeric data on patients’ characteristics and cases with adverse outcomes and employed inverse variance random‐effects models to derive pooled estimates.ResultsWe identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26‐4.41), acute cardiac (OR = 10.58, 5.00‐22.40) or kidney (OR = 5.13, 1.78‐14.83) injury, increased procalcitonin (OR = 4.8, 2.034‐11.31) or D‐dimer (OR = 3.7, 1.74‐7.89), and thrombocytopenia (OR = 6.23, 1.031‐37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D‐dimer conferred an increased risk of in‐hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934‐6.73), but not with mortality.ConclusionsAdvanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in‐hospital mortality.
Predictors of long‐term clinical remission in rheumatoid arthritis
Authors: Fornaro Marco , Cacciapaglia Fabio , Lopalco Giuseppe , Venerito Vincenzo , Iannone Florenzo 
Published: July 2020

AbstractAimLittle is known about possible predictors of long‐term survival on biologic disease‐modifying antirheumatic drugs (bDMARD) after achievement of deep clinical remission in rheumatoid arthritis (RA) patients. We aimed at assessing factors associated with drug persistence of the first bDMARD in RA patients who achieved Simplified Disease Activity Index (SDAI) remission.MethodsThe clinical charts of RA patients beginning a first bDMARD were retrospectively reviewed, and those who achieved SDAI‐based remission were selected for this analysis. Drug retention rate and mean survival time (MST) were estimated using Kaplan‐Meier curves, and hazard ratios (HRs) of discontinuing bDMARD were estimated by multivariate Cox‐regression models.ResultsEight‐six patients were on SDAI remission, and the survival rate of bDMARDs since ‘baseline‐time’ was 82.6% (MST = 77.8 (95% CI: 69‐86) months). Once on remission, patients not taking concomitant glucocorticoids had significantly higher survival rate (90.7%, MST = 86.3 (95% CI: 78‐95) months) than patients who continued to intake low dose of glucocorticoids (68.8%, MST = 56.9 (95% CI: 45‐69) months; P = .008). On the contrary, those patients assuming methotrexate (MTX) had significantly higher survival (87.7% (MST = 81.8 (95% CI: 73‐91) months) than patients who were not taking MTX (66.7% (MST = 55.3 (95% CI: 40‐71) months) (log‐rank 4.72, P = .03). After the achievement of disease remission, stopping glucocorticoids (HR 0.31, 95% CI: 0.10‐0.93) and methotrexate co‐therapy (HR 0.34, 95% CI: 0.12‐0.98) were independently associated with a lower risk of bDMARD discontinuation.ConclusionsAmong RA patients on clinical remission with a first bDMARD, those stopping glucocorticoids and continuing MTX had much longer survival on bDMARD.
Epidemiology, clinical characteristics of the first cases of COVID‐19
Authors: Liu Jialin , Liu Siru , Wei Hailong , Yang Xi 
Published: July 2020

AbstractBackgroundCOVID‐19 is currently the most urgent threat to public health in the world. The aim of this study is to provide an overview of the first cases of COVID‐19 to make further improvements in health policies and prevention measurements in response to the outbreak of COVID‐19.MethodsWe performed a search in PubMed, the CNKI (China National Knowledge Infrastructure), Web of Science and the WHO database of publications on COVID‐19 for peer‐reviewed papers from 1 December 2019 to 9 July 2020. We analysed the demographics, epidemiological characteristics, clinical features, signs and symptoms of the disease at the onset.ResultsWe identified the first cases of COVID‐19 in 16 different countries/regions from Asia, Europe, North America and South America. Of these 16 cases, 8 (50.0%) were male, with a mean of age 43.38 ± 15.19 years. All the cases had a history of travel or exposure. Twelve cases (75.0%) occurred in January, eight patients were Chinese, two patients were international students in Wuhan, one patient had a history of travelling in Wuhan, and one patient was in contact with Chinese patient. The longest hospital stay was 24 days (1 patient), and the shortest was 5 days (1 patient). The usual hospital stay was 9 days (4 patients).ConclusionUnderstanding the epidemiological characteristics, clinical characteristics, and diagnosis and treatment of the first patients in various countries are of great significance for the identification, prevention and control of COVID‐19.
Mapping the stocks in MICEX: Who is central in the Moscow Stock Exchange?
Authors: Hakan Eratalay M. , Vladimirov Evgenii V. 
Published: July 2020

AbstractIn this article, we use partial correlations to derive bi‐directional connections between major firms listed in the Moscow Stock Exchange. We obtain coefficients of partial correlation from the correlation estimates of the Constant Conditional Correlation GARCH (CCC‐GARCH) and the consistent Dynamic Conditional Correlation GARCH (cDCC‐GARCH) models. We map the graph of partial correlations using the Gaussian Graphical Model and apply network analysis to identify the most central firms in terms of both shock propagation and connectedness with others. Moreover we analyze some network characteristics over time and based on these we construct a measure of system vulnerability to external shocks. Our findings suggest that during the crisis interconnectedness between firms strengthens and becomes polarized and the system becomes more vulnerable to systemic shocks. In addition, we found that the most connected firms are the state‐owned firms Sberbank and Gazprom and the private oil company Lukoil, while in terms of the top most central systemic risk contributors, Sberbank gave its place to the NLMK Group.
First record of Ektaphelenchoides pini associated with Ips sexdentatus on Pinus nigra laricio in Italy
Authors: d'Errico Giada , Fanelli Elena , Troccoli Alberto , Binazzi Francesco , Landi Silvia , Roversi Pio , De Luca Francesca 
Published: July 2020

AbstractIn February 2015, an unexpected windstorm downed five hectares of a European black pine Pinus nigra subsp. laricio forest formation located close to Vallombrosa, Florence (Central Italy). In the following spring, an extensive survey was conducted in the area. Felled trees, stumps and all the suitable plant material were screened for the presence of the pinewood nematode (PWN), Bursaphelenchus xylophilus, by sampling wood and bark. Bark beetles were then collected from the gallery systems on the inner side of bark samples and observed in the laboratory. The following bark beetles were morphologically identified: Ips sexdentatus, Orthotomicus erosus, O. laricis and Pityogenes bidentatusa. The dissection of Ips sexdentatus allowed the extraction of numerous nematodes that were morphologically and molecularly identified as Ektaphelenchoides pini. Conversely, only few nematode specimens were isolated from either pine bark or wood. These individuals could be only molecularly identified and belonged to an undescribed nematode taxon. Even though no PWN was recorded in the investigated sites, our survey allowed the detection of a new association between E. pini and I. sexdentatus on P. nigra.
Maintained memory and long‐term potentiation in a mouse model of Alzheimer's disease with both amyloid pathology and human tau
Authors: Tulloch Jane , Netsyk Olga , Pickett Eleanor K. , Herrmann Abigail G. , Jain Pooja , Stevenson Anna J. , Oren Iris , Hardt Oliver , Spires‐Jones Tara L. 
Published: July 2020

AbstractOne of the key knowledge gaps in the field of Alzheimer's disease research is the lack of understanding of how amyloid beta and tau cooperate to cause neurodegeneration. We recently generated a mouse model (APP/PS1 + Tau) that develops amyloid plaque pathology and expresses human tau in the absence of endogenous murine tau. These mice exhibit an age‐related behavioural hyperactivity phenotype and transcriptional deficits which are ameliorated by tau transgene suppression. We hypothesized that these mice would also display memory and hippocampal synaptic plasticity deficits as has been reported for many plaque bearing mouse models which express endogenous mouse tau. We observed that our APP/PS1 + Tau model does not exhibit novel object memory or robust long‐term potentiation deficits with age, whereas the parent APP/PS1 line with mouse tau did develop the expected deficits. These data are important as they highlight potential functional differences between mouse and human tau and the need to use multiple models to fully understand Alzheimer's disease pathogenesis and develop effective therapeutic strategies.
“Multiplexing” cells of the visual cortex and the timing enigma of the binding problem
Authors: Zeki Semir 
Published: July 2020

AbstractIn this opinion essay, I address the perennial binding problem, that is to say of how independently processed visual attributes such as form, colour and motion are brought together to give us a unified and holistic picture of the visual world. A solution to this central issue in neurobiology remains as elusive as ever. No one knows today how it is implemented. The issue is not a new one and, though discussed most commonly in the context of the visual brain, it is not unique to it either. Karl Lashley summarized it well years ago when he wrote that a critical problem for brain studies is to understand how “the specialized areas of the cerebral cortex interact to provide the integration evident in thought and behaviour” (Lashley, 1931).
Assessment for Learning with Diverse Learners in a Digital World
Authors: DiCerbo Kristen 
Published: July 2020

AbstractWe have the ability to capture data from students' interactions with digital environments as they engage in learning activity. This provides the potential for a reimagining of assessment to one in which assessment become part of our natural education activity and can be used to support learning. These new data allow us to more closely examine the processes learners use to solve problems, not just their final solutions, so educators can be more targeted in their intervention. New capabilities may address some of the consistent criticisms of assessment, but they also present new dangers, particularly for diverse learners. Systems are in danger of replicating the biases from our non‐digital world in our digital tasks and in the creation of the scoring tools that accompany them.
Theanti‐geopoliticalcinematic eye: Documentary film and critical geopolitics
Authors: Holland Edward C. 
Published: July 2020

AbstractThis article considers documentary film as a format for critique and alternative viewings of the geopolitical. To do so, it reviews work in film studies on documentary film, emphasizing the theorization of the documentary ethos and the role of filmmakers in determining how documentaries depict reality. Identifying three points of consonance between documentary films and critical geopolitics, it reviews the geopolitical nature of many topical choices, the importance of authorial intent and creation, and the viewing of documentaries as texts whose interpretation is determined by their creators and viewers. The conclusion advocates for documentary film as a basis for a return to the consideration of format in critical geopolitics.
Infant growth during the first year of life following a pregnancy lifestyle intervention in routine care—Findings from the cluster‐randomisedGeliStrial
Authors: Hoffmann Julia , Günther Julia , Stecher Lynne , Spies Monika , Geyer Kristina , Raab Roxana , Meyer Dorothy , Rauh Kathrin , Hauner Hans 
Published: July 2020

SummaryBackgroundLifestyle interventions in pregnancy may influence postpartum development and obesity risk in offspring. The impact of lifestyle interventions as health system‐based approaches is unclear.ObjectiveTo evaluate the effect of an antenatal lifestyle intervention conducted as public health approach on infant development and feeding practices.MethodsWe followed offspring born to women participating in the cluster‐randomised GeliS trial who received usual care (CG) or repeated lifestyle counselling (IG). We collected data on offspring development and complementary feeding until the 12thmonth postpartum.ResultsOf the 1998 mother‐child pairs, 1783 completed the follow‐up. Mean infant weight at 12 months was comparable between groups (IG: 9497.9 ± 1137.0 g; CG: 9433.4 ± 1055.2 g;P= .177). There was no significant evidence of differences in sex‐ and age‐adjusted z‐scores or in the odds of offspring being overweight. More infants in the IG received whole‐grain products compared to the CG (95.6%vs. 90.8%;P= .003). Despite small differences in the timing of introducing solid foods, there were no further significant differences in the pattern of complementary feeding.ConclusionsThe antenatal lifestyle intervention embedded in routine care did not substantially influence infant anthropometrics and is thus unlikely to impact future development.
Large piezoelectricity and high Curie temperature in novel bismuth ferrite‐based ferroelectric ceramics
Authors: Yu Zhuo , Zeng Jiangtao , Zheng Liaoying , Liu Wenbing , Li Guorong , Kassiba Abdelhadi 
Published: July 2020

AbstractThe requirement for ferroelectric ceramics with a high Curie temperature and a high piezoelectric coefficient remains an important research task for high‐temperature sensors and actuators applications. (0.76‐x)BiFeO3‐0.24PbTiO3‐xBa(Sn0.2Ti0.8)O3 (BF‐PT‐BST) piezoelectric ceramics were fabricated using the solid‐state reaction method. XRD analysis indicated that the incorporation of large ionic radius Ba2+ at A‐site and nonferroelectric‐active Sn4+ at B‐site generated a decrease in the tetragonality degree c/a. A wide multiphase coexistence region was formed with the content of BST ranging from 0.13 to 0.28. The enhanced piezoelectric coefficient (d33 ~ 200pC/N) was achieved while maintaining a high Curie temperature (TC ~ 500°C) and a high depolarization temperature (Td ~ 450°C) for the composition of 0.6BF‐24PT‐0.16BST. TEM patterns provided clear evidence for the presence of nanodomains (~2nm) would be the predominant source for the enhanced piezoelectricity for the composition x = 0.20. The designed BF‐PT‐BST ternary system provides great potential for high‐temperature piezoelectric applications.
The interplay of individual differences, norms, and group identification in predicting prejudiced behavior in online video game interactions
Authors: Cary Lindsey A. , Axt Jordan , Chasteen Alison L. 
Published: July 2020

AbstractDespite the increasing popularity of video games and the diversity of people who play, prejudice remains common in online gaming. In the current study, we use structural equation modeling to test the role of social norms, individual differences, and gamer identification as predictors of how likely someone is to report engaging in prejudiced behavior while playing online video games. We also test the relative importance of these predictors to assess how likely people are to confront prejudice when it occurs in online video games. Participants (N = 384) completed a series of questionnaires to assess their attitudes and perceptions of online gaming norms, as well as to report their own prejudiced and confrontation behavior in video games. We found that both social norms and individual differences are significant predictors of behavior in online gaming. The more normative people report prejudice to be, the more they report making prejudiced comments. Similarly, the more normative confrontation of prejudice is reported to be, the more likely people are to report confronting prejudice. The more people endorsed generally prejudiced attitudes, the more likely they were to report making prejudiced remakes in online gaming and the less likely they were to report confronting prejudiced remarks. These results provide a foundation to inform interventions to reduce prejudice in gaming and indicate that both individual differences and norms are important to consider when designing interventions.
Knockdown of endogenous RNF4 exacerbates ischaemia‐induced cardiomyocyte apoptosis in mice
Authors: Qiu Fang , Han Yanna , Shao Xiaoqi , Paulo Petro , Li Wenyue , Zhu Mengying , Tang Nannan , Guo Shuaili , Chen Yibing , Wu Han , Zhao Dan , Liu Yu , Chu Wenfeng 
Published: July 2020

AbstractRNF4, a poly‐SUMO‐specific E3 ubiquitin ligase, is associated with protein degradation, DNA damage repair and tumour progression. However, the effect of RNF4 in cardiomyocytes remains to be explored. Here, we identified the alteration of RNF4 from ischaemic hearts and oxidative stress‐induced apoptotic cardiomyocytes. Upon myocardial infarction (MI) or H2O2/ATO treatment, RNF4 increased rapidly and then decreased gradually. PML SUMOylation and PML nuclear body (PML‐NB) formation first enhanced and then degraded upon oxidative stress. Reactive oxygen species (ROS) inhibitor was able to attenuate the elevation of RNF4 expression and PML SUMOylation. PML overexpression and RNF4 knockdown by small interfering RNA (siRNA) enhanced PML SUMOylation, promoted p53 recruitment and activation and exacerbated H2O2/ATO‐induced cardiomyocyte apoptosis which could be partially reversed by knockdown of p53. In vivo, knockdown of endogenous RNF4 via in vivo adeno‐associated virus infection deteriorated post‐MI structure remodelling including more extensive interstitial fibrosis and severely fractured and disordered structure. Furthermore, knockdown of RNF4 worsened ischaemia‐induced cardiac dysfunction of MI models. Our results reveal a novel myocardial apoptosis regulation model that is composed of RNF4, PML and p53. The modulation of these proteins may provide a new approach to tackling cardiac ischaemia.
The first reproductive parameters and evidence of multiple paternity in one new spiny dogfish species, Squalus albicaudus (Squaliformes, Squalidae)
Authors: Lamarca Felipe , Vianna Marcelo , Vilasboa Anderson 
Published: July 2020

AbstractUnderstanding elasmobranch reproductive biology is necessary for species conservation. Multiple paternity (MP) has been reported for elasmobranchs, and this study investigates the reproductive aspects and mating system (paternity genetic analyses) for Squalus albicaudus. Thirteen pregnant females were analysed concerning reproductive parameters, and the mating system was assessed for nine females and their litters. The study found a mean fecundity of 2.84 pups per litter without correlation between total female length and the number of embryos per litter. One litter showed evidence of MP, indicating the presence of polyandrous behaviour of the species.