bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lessons Learned Using Real‐World Data to Emulate Randomized Trials: A Case Study of Treatment Effectiveness for Newly Diagnosed Immune Thrombocytopenia
Authors: McGrath Leah J. , Nielson Carrie , Saul Bradley , Breskin Alexander , Yu Ying , Nicolaisen Sia K. , Kilpatrick Karynsa , Ghanima Waleed , Christiansen Christian F. , Bahmanyar Shahram , Linder Marie , Eisen Melissa , Wasser Jeffrey , Altomare Ivy , Kuter David , Sørensen Henrik T. , Kelsh Michael , Brookhart M. Alan 
Published: August 2021

Regulatory agencies are increasingly considering real‐world evidence (RWE) to support label expansions of approved medicines. We conducted a comparative effectiveness study to emulate a proposed randomized trial of romiplostim vs. standard‐of‐care (SOC) therapy among patients with recently diagnosed (≤12 months) immune thrombocytopenia (ITP), that could support expansion of the romiplostim label. We discuss challenges that we encountered and solutions that were developed to address those challenges. Study size was a primary concern, particularly for romiplostim initiators, given the rarity of ITP and the stringent trial eligibility criteria. For this reason, we leveraged multiple data sources (Nordic Country Patient Registry for Romiplostim; chart review study of romiplostim initiators in Europe; Flatiron Health EMR linked with MarketScan claims). Additionally, unlike the strictly controlled clinical trial setting, platelet counts were not measured at regular intervals in the observational data sources, and therefore the end point of durable platelet response often used in trials could not be reliably measured. Instead, the median platelet count was chosen as the primary end point. Ultimately, while we observed a slightly higher median platelet count in the romiplostim group vs. SOC, precision was limited because of small study size (median difference was 11 × 109/L (95% CI: −59, 81)). We underscore the importance of conducting comprehensive feasibility assessments to identify fit‐for‐purpose data sources with sufficient sample size, data elements, and follow‐up. Beyond technical challenges, we also discuss approaches to increase the credibility of RWE, including systematic incorporation of clinical expertise into study design decisions, and separation between decision makers and the data.
A novel bias compensation recursive least square‐multiple weighted dual extended Kalman filtering method for accurate state‐of‐charge and state‐of‐health co‐estimation of lithium‐ion batteries
Authors: Qiao Jialu , Wang Shunli , Yu Chunmei , Shi Weihao , Fernandez Carlos 
Published: August 2021

AbstractState‐of‐charge and state‐of‐health of power lithium‐ion batteries are two important state parameters for battery management system monitoring. To accurately estimate the state‐of‐charge and state‐of‐health of in real time, the ternary lithium‐ion battery is taken as the research object, and a novel bias compensation recursive least square‐multiple weighted dual extended Kalman filtering method is proposed innovatively. The noise variance estimation is introduced to compensate the parameters identified by the general least square method to realize the accurate identification. The estimation value is corrected by using the residual and Kalman gain at multiple times, and different weights are configured for each residual according to the amount of information contained. The data of different complex conditions are used to verify the feasibility of the proposed algorithm, the results show that the root‐mean‐square error of bias compensation recursive least square‐multiple weighted dual extended Kalman filtering under dynamic stress test and Beijing bus dynamic stress test condition can be controlled within 1.62% and 2.70% in state‐of‐charge estimation, 0.17% and 0.81% in state‐of‐health estimation, which verifies that the proposed algorithm in this research has good running effect. The novel bias compensation recursive least square‐multiple weighted dual extended Kalman filtering method lays a theoretical foundation for the safe operation of electric vehicles.
High vagal tone and rapid extinction learning as potential transdiagnostic protective factors following childhood violence exposure
Authors: Susman Eli S. , Weissman David G. , Sheridan Margaret A. , McLaughlin Katie A. 
Published: August 2021

AbstractChildhood exposure to violence is strongly associated with psychopathology. High resting respiratory sinus arrhythmia (RSA) is associated with lower levels of psychopathology in children exposed to violence. High RSA may help to protect against psychopathology by facilitating fear extinction learning, allowing more flexible autonomic responses to learned threat and safety cues. In this study, 165 youth (79 female, aged 9–17; 86 exposed to violence) completed assessments of violence exposure, RSA, and psychopathology, and a fear extinction learning task; 134 participants returned and completed psychopathology assessments 2 years later. Resting RSA moderated the longitudinal association of violence exposure with post‐traumatic stress disorder (PTSD) symptoms and externalizing psychopathology, such that the association was weaker among youths with higher RSA. Higher skin conductance responses (SCR) during extinction learning to the threat cue (CS+) was associated with higher internalizing symptoms at follow‐up and greater SCR to the safety cue (CS–) was associated with higher PTSD, internalizing, and externalizing symptoms, as well as the p‐factor, controlling for baseline symptoms. Findings suggest that higher RSA may protect against emergence of psychopathology among children exposed to violence. Moreover, difficulty extinguishing learned threat responses and elevated autonomic responses to safety cues may be associated with risk for future psychopathology.
Links between socioeconomic disadvantage, neural function, and working memory in early childhood
Authors: Li Xinge , Lipschutz Rebecca , Hernandez Samuel Montero , Biekman Brian , Shen Shutian , Montgomery Diana A. , Perlman Susan B. , Pollonini Luca , Bick Johanna 
Published: August 2021

AbstractChildren reared in socioeconomically disadvantaged environments are at risk for academic, cognitive, and behavioral problems. Mounting evidence suggests that childhood adversities, encountered at disproportionate rates in contexts of socioeconomic risk, shape the developing brain in ways that explain disparities. Circuitries that subserve neurocognitive functions related to memory, attention, and cognitive control are especially affected. However, most work showing altered neural function has focused on middle childhood and adolescence. Understanding alterations in brain development during foundational points in early childhood is a key next step. To address this gap, we examined functional near‐infrared‐spectroscopy‐based neural activation during a working memory (WM) task in young children aged 4–7 years (N = 30) who varied in socioeconomic risk exposure. Children who experienced greater disadvantage (lower income to needs ratio and lower Hollingshead index) exhibited lower activation in the lateral prefrontal cortex than children who experienced less to no disadvantage. Variability in prefrontal cortex activation, but not behavioral performance on the WM task, was associated with worse executive functioning in children as reported by parents. These findings add to existing evidence that exposure to early adversity, such as socioeconomic risk, may lead to foundational changes in the developing brain, which increases risk for disparities in functioning across multiple cognitive and social domains.
Restoration of species‐rich grasslands by transfer of local plant material and its impact on species diversity and genetic variation—Findings of a practical restoration project in southeastern Germany
Authors: Kaulfuß Franziska , Reisch Christoph 
Published: August 2021

AbstractRestoration of species‐rich grasslands is a key issue of conservation. The transfer of seed‐containing local plant material is a proven technique to restore species‐rich grassland, since it potentially allows to establish genetically variable and locally adapted populations. In our study, we tested how the transfer of local plant material affected the species diversity and composition of restored grasslands and the genetic variation of the typical grassland plant species Knautia arvensis and Plantago lanceolata.For our study, we selected fifteen study sites in southeastern Germany. We analyzed species diversity and composition and used molecular markers to investigate genetic variation within and among populations of the study species from grasslands that served as source sites for restoration and grasslands, which were restored by transfer of green hay and threshed local plant material.The results revealed no significant differences in species diversity and composition between grasslands at source and restoration sites. Levels of genetic variation within populations of the study species Knautia arvensis and Plantago lanceolata were comparable at source and restoration sites and genetic variation among populations at source and their corresponding restoration sites were only marginal different.Our study suggests that the transfer of local plant material is a restoration approach highly suited to preserve the composition of species‐rich grasslands and the natural genetic pattern of typical grassland plant species.
Impact of Oreochromis niloticus (Linnaeus, 1758) (Pisces: Cichlidae) invasion on taxonomic and functional diversity of native fish species in the upper Kabompo River, northwest of Zambia
Authors: Jere Arthertone , Jere Wilson W. L. , Mtethiwa Austin , Kassam Daud 
Published: August 2021

AbstractInvasive alien species have been revealed to drastically alter the structure of native communities; however, there is scarce information on whether taxonomic and functional spaces occupied by native species are equally filled by exotic species. We investigated the diversity of native species to understand the impact of exotic Oreochromis niloticus in the upper Kabompo River, northwest of Zambia using taxonomic and functional diversity indices. To achieve this, two tests were performed (Test 1, compared natives in invaded and uninvaded sections; Test 2, compared natives in invaded section). A total of 17 species were collected for functional diversity computation, out of which fourteen (14) functional trait measurements linked to feeding, locomotion, and life history strategy were taken. Findings revealed that taxonomic and functional diversity values changed with invasion in both tests. Taxonomic diversity was 15% more in invaded than uninvaded sections in Test 1 and was not consistent across sampling points of invaded section in Test 2. Invaded areas were taxonomically less diverse, but functionally diverse in both tests. The analysis of similarity and nonmetric multidimensional scaling revealed no difference in Bray–Curtis similarity assemblages in both tests. Our findings revealed that exotic species more often occupy unfilled gaps in the communities often occupied by the native species; this is achieved by occupying functional spaces. Overall, changes in taxonomic and functional diversity of native species documented here partially confirmed impacts of O. niloticus invasion. Therefore, we recommend a multifaceted approach to assess cumulative impacts of invasion on native species.
Intensity and mode of Lindera melissifolia reproduction are affected by flooding and light availability
Authors: Leininger Theodor D. , Gardiner Emile S. , Lockhart Brian Roy , Schiff Nathan M. , Wilson Alphus Dan , Devall Margaret S. , Hamel Paul B. , Connor Kristina F. 
Published: August 2021

AbstractWe studied the impact of flooding and light availability gradients on sexual and asexual reproduction in Lindera melissifolia (Walt.) Blume, an endangered shrub found in floodplain forests of the Mississippi Alluvial Valley (MAV), USA. A water impoundment facility was used to control the duration of soil flooding (0, 45, or 90 days), and shade houses were used to control light availability (high = 72%, intermediate = 33%, or low = 2% of ambient light) received by L. melissifolia established on native soil of the MAV. Sexual reproductive intensity, as measured by inflorescence bud count, fruit set, and drupe production, was greatest in the absence of soil flooding. Ninety days of soil flooding in the year prior to anthesis decreased inflorescence bud counts, and 45 days of soil flooding in the year of anthesis lessened fruit set and drupe production. Inflorescence bud development was the greatest in environments of intermediate light, decreased in high‐light environments, and was absent in low light environments. But low fruit set diminished drupe production in intermediate light environments as compared to high light environments. Asexual reproduction, as measured by development of new ramets, was greatest in the absence of soil flooding and where plants were grown in high or intermediate light. Plants exhibited plasticity in reproductive mode such that soil flooding increased the relative importance of asexual reproduction. The high light environment was most favorable to sexual reproduction, and reproductive mode transitioned to exclusively asexual in the low light environment. Our results raise several implications important to active management for the conservation of this imperiled plant.
Long‐term trophic state responses of a large tropical coastal lagoon to land use changes and nutrient transport
Authors: Campaneli Leonardo Bernardo , Rezende Carlos Eduardo de , Lacerda Luiz Drude de , Almeida Marcelo Gomes , Molisani Mauricio Mussi 
Published: August 2021

AbstractThe watershed of a large tropical coastal lagoon, historically hosting large sugarcane crops, which has been reduced during the last decades. It suggests that land use and land cover changes (LULCC) would lower the trophic state of the coastal lagoon due to less fertilization application and consequently reducing nutrient transfer into the lagoon. In this context, this study assessed the influence of LULCC, represented by the reduction of the sugarcane crops on the trophic state of a large tropical coastal lagoon. This influence was assessed by means of information about the long‐term overall mass‐balance budget, involving the estimation of the N and P loads from the sugarcane crops, other anthropogenic sources and natural processes; measurements of the river N and P fluxes into the lagoon; its seaward outflow and the long‐term lacustrine nutrient retention. The results indicate that sugarcane crop reduction represented a decrease of 686 t of N and 51 t of P being emitted to the lagoon watershed. However, N and P loads from sugarcane crops were partially replaced by other anthropogenic activities, but even with the reduction of the nutrient fluxes, the long‐term supereutrophic responses of the coastal lagoon was maintained. The sediment‐related C/N and isotopic composition of the lagoon was sensitive to LULCC, indicating changes on the organic matter inputs into the lagoon. The trophic state was also influenced by the soil N and P accumulation and the long‐term nutrient retention within the lagoon imposed by its restricted water connection to the sea.
Quantifying the diet diversity of herbivorous coral reef fishes using systematic review and DNA metabarcoding
Authors: Nalley Eileen M. , Donahue Megan J. , Heenan Adel , Toonen Robert J. 
Published: August 2021

AbstractHerbivorous reef fishes are an important component of coral reef ecosystems and a focal point in reef management. Herbivore diets have been examined using a myriad of methods, making it difficult to compare between analyses and to examine consistency or variability in diet across large spatial scales or heterogeneous environments. Here, we present a method to quantify and validate the diet diversity of these important coral reef species. We compile a database of information on Pacific herbivorous reef fishes through a systematic review of published diet data, and for those studies in which appropriate information is reported, we calculate a single Simpson's Diversity Index value to represent the diet diversity of each. We then validate this approach by examining the diet diversity of five species using DNA metabarcoding to sequence the algae present in their stomach contents. The two approaches provided comparable estimates of diet diversity, and we find evidence for considerable diet variability both within functional groups and between closely related species. Although there is a wide range of diet specialization within each functional and taxonomic group, parrotfishes and detritivorous surgeonfishes appear to have more limited diets than other nominal herbivorous fishes in our survey. This may make them more vulnerable to habitat degradation, which is important considering that both groups face considerable fishing pressure in Hawaiʻi and elsewhere in the Pacific. Finally, we demonstrate how this approach to quantifying diet can be incorporated into trait matrices that offer valuable insight into the dissimilarity between species, regardless of their taxonomic and functional classification. This analysis offers a simplified quantitative index of diet diversity that can contribute to better management of herbivores and increased understanding of their functional effects on changing, degraded reefs.
Outcome of patients with non‐ischaemic cardiogenic shock supported by percutaneous left ventricular assist device
Authors: Haurand Jean M. , Haberkorn Sandra , Haschemi Jafer , Oehler Daniel , Aubin Hug , Akhyari Payam , Boeken Udo , Kelm Malte , Westenfeld Ralf , Horn Patrick 
Published: August 2021

AbstractAimsPercutaneous left ventricular assist devices (pVADs) are used to haemodynamically stabilize patients with cardiogenic shock (CS) caused by acute myocardial infarction (AMI). One out of every two patients has a non‐ischaemic cause of CS, and these patients differ profoundly from patients with AMI‐related CS. We assessed the usefulness of pVAD support for patients with non‐ischaemic CS.Methods and resultsWe analysed 106 patients with CS and Impella® support between 2015 and 2018. CS was non‐ischaemic in 36 patients and AMI‐related in 70 patients. Compared with the AMI group, those in the non‐ischaemic group were significantly younger [median age 62 (50.8, 70.8) years vs. 68 (58.0, 75.5) years, P = 0.007] and had more patients with severely reduced left ventricular function (94% vs. 79%, P = 0.035) and worse glomerular filtration rate [45 (27, 57) mL/min vs. 60 (44, 78) mL/min]. Propensity score matching yielded 31 patients with non‐ischaemic CS and 31 patients with AMI‐related CS, without a difference in baseline laboratory values or comorbidities. In both groups, pVAD support was performed along with haemodynamic stabilization, reduction of catecholamines and normalization of lactate levels. In 7 days, systolic blood pressure increased from 91 (80, 101) mmHg at baseline to 100 (100, 120) mmHg in the non‐ischaemic CS group (P = 0.001) and 89 (80, 100) mmHg at baseline to 112 (100, 128) mmHg in the AMI‐related CS group (P = 0.001). Moreover, in 7 days, the need of catecholamines (calculated as vasoactive‐inotropic score) decreased from 32.0 (11.1, 47.0) at baseline to 5.3 (0, 16.1) in the non‐ischaemic group (P = 0.001) and from 35.2 (18.11, 67.0) to zero (0, 0) in the AMI‐related CS group (P = 0.001). Lactate level decreased from 3.8 (2.8, 5.9) mmol/L at baseline to 1.0 (0.8, 2.1) mmol/L (P = 0.001) in the non‐ischaemic CS group and from 3.8 (2.6, 6.5) mmol/L to 1.2 (1.0, 2.0) mmol/L in the AMI‐related group (P = 0.001).In the non‐ischaemic CS group, eight patients (25.8%) were upgraded to veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) or long‐term mechanical circulatory support. Two of these upgraded patients received heart transplantation. In the AMI group, eight patients (25.8%) were upgraded to VA‐ECMO or long‐term mechanical circulatory support. Ninety‐day survival did not significantly differ between the groups (non‐ischaemic CS group 48.4%, AMI‐related CS group 45.2%, P = 0.799).ConclusionspVAD support is useful for haemodynamic stabilization of patients with non‐ischaemic CS and is valuable as a bridge to patients' recovery or long‐term left ventricular support and heart transplantation.
Synthesis of Open‐Cage Fullerenes with Pyrrole, Pyrrolone, Pyridinone, Iminofuran, and Pyranone Fragments Embedded on the Rim of the Orifice
Authors: Liu Zhen , Gao Rui , Liu Zeyu , Xia Zongpu , Liu Xueli , Ming Jialin , Wang Xiaoge , Su Jie , Gan Liangbing 
Published: August 2021

AbstractAn open‐cage fullerene derivative with a pyranone and a diiminopentanone moiety was prepared. Further reaction with aniline could convert the pyranone moiety into a pyrrole moiety through the pyridinone moiety as an intermediate. During the process, decarboxylation and dehydroxylation aromatization reactions also took place on the diiminopentanone moiety and the two adjacent hydroxyl groups, thus forming iminofuran or pyrrolone moiety on the rim of the open‐cage fullerene. Protonation experiment showed that the imino nitrogen atom on the rim of the orifice is more basic than the pyrrole nitrogen atom. The lone pair of the pyrrole nitrogen is partially conjugated with the π system of the fullerene cage as shown by single crystal X‐ray structures.
Voltammetric Determination of Hesperidin on the Electrode Modified with SnO2 Nanoparticles and Surfactants
Authors: Ziyatdinova Guzel , Yakupova Elvira , Davletshin Rustam 
Published: August 2021

AbstractHighly sensitive voltammetric method for hesperidin determination is developed using glassy carbon electrode modified with SnO2 nanoparticles (SnO2 NPs) and surfactants. The highest oxidation currents of hesperidin are observed in the case of cationic 0.50 mM cetylpyridinium bromide (CPB). Parameters of hesperidin electrooxidation have been calculated. Adsorptive anodic differential pulse voltammetry (AdADPV) in phosphate buffer pH 7.0 after 120 s accumulation provides linear dynamic ranges of 0.10–10 and 10–75 μM with the detection limit of 0.077 μM. The selectivity of hesperidin response is proved in the presence of inorganic ions, saccharides, ascorbic acid and other natural phenolics.
AOP Report: Uncoupling of Oxidative Phosphorylation Leading to Growth Inhibition via Decreased Cell Proliferation
Authors: Song You , Villeneuve Daniel L. 
Published: August 2021

ABSTRACT
This report describes a novel adverse outcome pathway (AOP) on uncoupling of oxidative phosphorylation (OXPHOS) leading to growth inhibition via decreased adenosine triphosphate (ATP) pool and cell proliferation (AOPWiki, AOP263). Oxidative phosphorylation is a major metabolic process that produces the primary form of energy (ATP) supporting various biological functions. Uncoupling of OXPHOS is a widely recognized mode of action of many chemicals and is known to affect growth via different biological processes. Capturing these events in an AOP can greatly facilitate mechanistic understanding and hazard assessment of OXPHOS uncouplers and growth regulators in eukaryotes. The four proposed key events in this AOP are intentionally generalized to cover a wide range of organisms and stressors. Three out of four events can be measured using in vitro high-throughput bioassays, whereas for most organisms, growth inhibition can also be measured in a high-throughput format using standard in vivo toxicity test protocols. The key events and key event relationships in this AOP are further assessed for weight of evidence using evolved Bradford-Hill considerations. The overall confidence levels range from moderate to high with only a few uncertainties and inconsistencies. The chemical applicability domain of the AOP mainly contains protonophores uncouplers, which can be predicated using the quantitative structure-activity relationship (QSAR) approach and validated using in vitro high-throughput bioassays. The biological domain of the AOP basically covers all eukaryotes. The AOP described in this report is part of a larger AOP network linking uncoupling of OXPHOS to growth inhibition, and is considered highly relevant and applicable to both human health and ecological risk assessments.