bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear mixed models and geostatistics for designed experiments in soil science: Two entirely different methods or two sides of the same coin?
Authors: Slaets Johanna I. F. , Boeddinghaus Runa S. , Piepho Hans‐Peter 
Published: April 2020

AbstractSoil scientists are accustomed to geostatistical methods and tools such as semivariograms and kriging for analysis of observational data. Such methods assume and exploit that observations are spatially correlated. Conversely, analysis of variance (ANOVA) of designed experiments assumes that observations from different experimental units are independent, an assumption that is justified based on randomization. It may be beneficial, however, to perform an ANOVA assuming a geostatistical covariance model. Also, it is increasingly common to have multiple observations per experimental unit. Simple ANOVA assuming independence of observations is not appropriate for such data. Instead, a linear mixed model accounting for correlation among observations made on the same plot is required for proper analysis. The purpose of this paper is to demonstrate the benefits of integrating geostatistical covariance structures and ANOVA procedures into a linear mixed modelling framework. Two examples from designed experiments are considered in detail, making a link between terminologies and jargon used in geostatistical analysis on the one hand and linear mixed modelling on the other hand. We provide code in R and SAS for both examples in two supporting companion documents.Highlights
Analysis of variance and geostatistical analysis can be joined in a mixed model.
Randomization justifies the independence assumption in analysis of variance.
Geostatistical models imply a correlation of errors and can improve efficiency.
Lacking randomization, spatial correlation can be accounted for in a mixed model.
Patient‐centredness in acute stroke care – a qualitative study from the perspectives of patients, relatives and staff
Authors: Busetto L. , Stang C. , Hoffmann J. , Amiri H. , Seker F. , Purrucker J. , Ringleb P. A. , Nagel S. , Bendszus M. , Wick W. , Gumbinger C. ,   for the Stroke Consortium Rhine‐Neckar
Published: April 2020

Background and purposeAlthough patient‐centredness is considered a key component of high‐quality neurological care, it is unclear to what extent it can or should be implemented during the acute phase. Using acute stroke as an example, the aim was to identify critical junctures for patient‐centredness along the acute care pathway from the perspectives of patients, relatives and staff.MethodsA qualitative multi‐method study was conducted including 27 non‐participant observations and 37 semi‐structured interviews with patients, relatives and staff. Junctures were defined as critical when mentioned (as problematic) in two or three information sources (i.e. observations, staff interviews, or patient and relative interviews), as potentially critical when mentioned in one, and as uncritical when not mentioned.ResultsPost‐procedure communication after thrombectomy, patients’ stay at the stroke unit and decision‐making around transfer, discharge and rehabilitation were identified as critical junctures for patient‐centredness. Arrival at the emergency department and the (thrombectomy) treatment itself were identified as uncritical junctures, whilst history‐taking and treatment preparation, the treatment decision and patients’ stay at the intensive care unit were identified as potentially critical junctures.ConclusionsIn acute stroke care, patients, relatives and staff prioritize fast over patient‐centred decision‐making in the most time‐critical phases, especially before and during treatment. This is reversed after the procedure, when difficulties arise implementing a patient‐centred approach in clinical practice. To improve patient‐centredness where it is most needed, clear guidelines and accessible resources are recommended. Future research should investigate whether insights from acute phases of stroke care are applicable to other neurological conditions as well.
Pharmacokinetics and safety of VALTOCO (NRL‐1; diazepam nasal spray) in patients with epilepsy during seizure (ictal/peri‐ictal) and nonseizure (interictal) conditions: A phase 1, open‐label study
Authors: Hogan Robert Edward , Tarquinio Daniel , Sperling Michael R. , Klein Pavel , Miller Ian , Segal Eric B. , Rabinowicz Adrian L. , Carrazana Enrique 
Published: April 2020

AbstractObjectiveTo assess pharmacokinetics and safety of diazepam nasal spray (NRL‐1; VALTOCO®) in pediatric and adult patients with epilepsy in seizure and nonseizure states.MethodsA single dose of diazepam nasal spray (5, 10, 15, or 20 mg based on weight) was administered during each of two conditions (ictal/peri‐ictal and interictal condition) to patients 6‐65 years old with partial or generalized epilepsy with motor seizures or seizures with clear alteration of awareness; a second dose was permitted if needed for persistent seizures. Dosing could be interictal or ictal/peri‐ictal first, with a washout of ≥14 days. Blood samples for pharmacokinetic analysis were taken at prespecified time points. Treatment‐emergent adverse events (TEAEs), sedation, nasal irritation, nasal mucosal pain, and olfactory changes were assessed.ResultsOf 57 patients in the study (mean age = 28.1 years [range = 6‐59], 54.4% female, 80.7% white), 49 were included in the primary pharmacokinetic analyses. Diazepam pharmacokinetic profiles were similar under both conditions, with approximately 2‐hour median time to mean (SD) maximum plasma concentrations of 164 (88) and 189 (110) ng/mL for ictal/peri‐ictal and interictal conditions, respectively; drug exposure during the first 6 hours postdosing was 532 (313) and 615 (368) h•ng/mL, respectively. Seventeen patients (29.8%) reported TEAEs, of whom eight (14%) had treatment‐related TEAEs, with those reported in ≥2 patients being dysgeusia (n = 3, 5.3%) and nasal discomfort (n = 2, 3.5%). One patient had serious TEAEs (recurrent seizures, metabolic encephalopathy), which were deemed unrelated to study treatment. No changes in respiratory rate were observed, nor were there clinically relevant changes in sedation, olfaction, nasal irritation, or acute nasal mucosal pain.SignificanceThe epileptic conditions (ictal/peri‐ictal, interictal) had minimal impact on diazepam nasal spray pharmacokinetics in patients with epilepsy. Therefore, diazepam nasal spray can be administered ictally and interictally. Diazepam nasal spray safety was consistent with the profile of diazepam.
Insoluble tau aggregates induce neuronal death through modification of membrane ion conductance, activation of voltage‐gated calcium channels and NADPH oxidase
Authors: Esteras Noemi , Kundel Franziska , Amodeo Giuseppe F. , Pavlov Evgeny V. , Klenerman David , Abramov Andrey Y. 
Published: April 2020

Most neurodegenerative disorders are associated with aggregation and accumulation of misfolded proteins. One of these proteins, tau, is involved in a number of pathologies including Alzheimer's disease and frontotemporal dementia. Aggregation and phosphorylation of tau have been shown to be a trigger for abnormal signal transduction and disruption of cellular homeostasis. Here, we have studied the effect of extracellular tau at different stages of aggregation in cortical co‐cultures of neurons and astrocytes, to understand how this process affects tau pathogenicity. We found that the species formed after prolonged in vitro aggregation of tau (longer than 1 day) are able to stimulate reactive oxygen species (ROS) production through the activation of NADPH oxidase without decreasing the level of the endogenous antioxidant glutathione. The same late insoluble aggregates of tau induced calcium signals in neurons and a gradual increase in the ionic current of artificial membranes. Both tau‐induced calcium signals and ROS production in NADPH oxidase were reduced in the presence of the inhibitor of voltage‐gated calcium channels (VGCC) nifedipine. This suggests that insoluble aggregates of tau incorporate into the membrane and modify ionic currents, changing plasma membrane potential and activating VGCCs, which induces a calcium influx that triggers ROS production in NADPH oxidase. The combination of all these effects likely leads to toxicity, as only the same insoluble tau aggregates which demonstrated membrane‐active properties produced neuronal cell death.
Animal and forage responses on lucerne (Medicago sativa L.) pastures under contrasting grazing managements in a temperate climate
Authors: Berone Germán D. , Sardiña María C. , Moot Derrick J. 
Published: April 2020

AbstractThis study determined the impact of a change in grazing system on beef production from lucerne pastures in Argentina. One system (T500) used the traditional recommendation to commence grazing in spring when lucerne was near to 10% flowering. The grazing interval was ~ 500 growing degree‐days (GDD; above a base temperature for growth of 5°C) from mid‐spring to mid‐autumn. In contrast, the T350 system commenced grazing 11–15 days earlier at ~ 1,000 kg DM/ha and the grazing interval was ~ 350 GDD from mid‐spring to mid‐summer, and from mid‐summer to mid‐autumn, it was ~ 500 GDD. Total live‐weight production was ~ 30% or 185 and 115 kg/ha higher in T350 than T500 in Years 1 and 2 respectively. This was due to a higher live‐weight production per head and a higher stocking rate, because T350 produced 1,600 kg DM ha−1 year−1 more forage. Plant population (~70 plants/m2) and perennial biomass (root plus crown) at the end of the second year did not differ between treatments. This suggests that lucerne persistence was not affected by the more intensive spring grazing of T350, because an adequate period of autumn recovery was allowed. This work quantified the live‐weight gain (+30%, +150 kg/ha) when the grazing management of lucerne during the spring–summer period was based on crop growth status (i.e. standing biomass, canopy height) rather than on crop phenology.
Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study
Authors: Veen Caroline S. B. , Huisman Elise J. , Cnossen Marjon H. , Kom‐Gortat Regina , Rijken Dingeman C. , Leebeek Frank W. G. , de Maat Moniek P. M. , Kruip Marieke J. H. A. 
Published: April 2020

AbstractIntroductionDiagnostic evaluation of patients with a bleeding tendency remains challenging, as no disorder is identified in approximately 50% of patients. An impaired interplay of several haemostatic factors might explain bleeding phenotype in these patients.ObjectiveTo investigate whether global haemostasis assays are able to identify haemostatic abnormalities in patients with a bleeding tendency unexplained by current diagnostic laboratory tests.Materials and methodsPatients of ≥12 years with a bleeding tendency were included from a tertiary outpatient clinic. Bleeding phenotype was assessed with the ISTH‐BAT. Patients were classified as having bleeding of unknown cause (BUC) or a mild bleeding disorder (MBD) based on abnormalities assessed by routine haemostatic tests. Global haemostasis tests (rotational thromboelastometry (ROTEM), thrombin generation test (TG) and plasma clot lysis time (CLT)) were measured in all patients. The results were compared with 76 controls.ResultsOne hundred and eighty‐one patients were included, and 60% (109/181) was classified as having BUC. BUC patients demonstrated a significantly prolonged lag time in TG (median 7.7 minutes, IQR 6.7‐8.7) and a significantly prolonged CLT (median 60.5 minutes, IQR 54.7‐66.1) compared to controls. No differences in ROTEM variables were found. Patients with MBD showed an impaired thrombin generation with a significantly decreased ETP (median 1024 nmol/L*min, IQR 776‐1355) and peak height (median 95 nmol/L, IQR 76‐138), compared to BUC patients and controls.ConclusionNo major differences were found in ROTEM and TG variables in BUC patients compared to controls. BUC patients did have a significantly prolonged clot lysis time. The underlying mechanism for this finding is unknown.
Depressive symptoms and adherence to prophylaxis in patients with haemophilia from Croatia and Slovenia
Authors: Bago Martina , Butkovic Ana , Preloznik Zupan Irena , Faganel Kotnik Barbara , Prga Ivana , Bacic Vrca Vesna , Zupancic Salek Silva 
Published: April 2020

IntroductionAdherence to a prophylactic therapy is obligatory to prevent bleeding in patients with haemophilia. It has already been recognized that depression is associated with treatment adherence.AimThe aim of this study was to examine the prevalence of depressive symptoms in adults with haemophilia using an instrument designed or validated for diagnosing or screening for depression and to investigate the association of symptoms of depression with nonadherence to prophylactic therapy in patients from two East European countries.MethodsAdult patients with severe or moderate haemophilia receiving prophylaxis were eligible for the study. Depressive symptoms were assessed with BDI‐II, adherence with VERITAS‐Pro, demographic and socioeconomic data were collected using a questionnaire, and clinical data were obtained from medical records.ResultsFinal sample included 81 participants (median age was 45 years, range 18‐73 years). There were 9 (11%) participants with scores on BDI‐II above 14 points, the cut‐off score for depressive symptomatology. In general, participants were adherent. However, there were 14 (17%) participants who had scores above 57 points, the cut‐off score for nonadherence. There was an association between having depressive symptoms and being nonadherent, and depressive symptoms explained additional variance in adherence after controlling for sociodemographic, psychosocial and clinical characteristics.ConclusionSince there is an association between depressive symptoms and nonadherence, it would be beneficial for both patients and the public health system for screening for depressive symptoms to be included as a part of the treatment protocol.
Diagnostic accuracy of FibroScan‐AST score to identify non‐alcoholic steatohepatitis with significant activity and fibrosis in Japanese patients with non‐alcoholic fatty liver disease: Comparison between M and XL probes
Authors: Oeda Satoshi , Takahashi Hirokazu , Imajo Kento , Seko Yuya , Kobayashi Takashi , Ogawa Yuji , Moriguchi Michihisa , Yoneda Masato , Anzai Keizo , Irie Hiroyuki , Sueoka Eisaburo , Aishima Shinichi , Kage Masayoshi , Itoh Yoshito , Eguchi Yuichiro , Nakajima Atsushi 
Published: April 2020

AimRecently, FibroScan‐AST (FAST) score was reported to be effective for identifying non‐alcoholic steatohepatitis (NASH) with significant activity and fibrosis in non‐alcoholic fatty liver disease (NAFLD). The aim of this study was to confirm the diagnostic accuracy of FAST score of Japanese patients and compare the cut‐off values and diagnostic accuracy between the FibroScan M and XL probes.MethodsEighty‐two and 84 patients were included the verification and validation sets, respectively. All patients were diagnosed with NAFLD by biopsy by two central expert pathologists. Liver stiffness measurements and controlled attenuation parameter were carried out, and diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsNo significant difference existed in FAST score between the M and XL probes (0.489 vs. 0.483, P = 0.187). No significant difference existed in the area under the ROC between the two probes (M, 0.7598; XL, 0.7614; P = 0.958). According to the Youden index, the cut‐off value using the M probe was 0.57 with 68.2% sensitivity and 78.3% specificity. For the XL probe, the cut‐off value was 0.56 with 68.2% sensitivity and 73.3% specificity. To obtain sensitivity and specificity values higher than 90%, cut‐off values of 0.35 and 0.66 were chosen for the M probe and 0.32 and 0.63 were chosen for the XL probe.ConclusionsThere was no significant difference in diagnostic accuracy of FAST score between the FibroScan M and XL probes. The FAST score can be used to identify NASH with significant risk in Japanese patients regardless of probe selection.
Maternal knowledge, stimulation, and early childhood development in low‐income families in Colombia
Authors: Cuartas Jorge , Rey‐Guerra Catalina , McCoy Dana Charles , Hanno Emily 
Published: April 2020

AbstractTheoretical models assume that parental knowledge about child development and caregiving motivates parental stimulation, shaping child development. Evidence supporting these models is scarce in low‐ and middle‐income countries (LMICs). This study tests the relations between maternal knowledge, stimulation, and child development in a Colombian sample of 1,277 low‐income mothers and their children under the age of five. Mothers showed diverse knowledge about child development and caregiving. Moreover, maternal knowledge when children were 9–26 months old indirectly predicted growth in children's cognitive, receptive language, and gross motor skills at ages 27–46 months, partially through maternal engagement in stimulating activities with the child.
Predictors of oral health promotion behaviors among elementary school children: Examination of an extended social cognitive theory
Authors: Bashirian Saeed , Seyedzadeh‐Sabounchi Shabnam , Shirahmadi Samane , Karimi‐Shahanjarini Akram , Soltanian Ali Reza , Vahdatinia Farshid 
Published: April 2020

AbstractBackgroundBrushing teeth with fluoride‐containing toothpaste and flossing are considered as effective solutions for preventing dental caries and periodontal diseases.AimThe aim of this study was to use the promoted social cognitive theory (SCT) to investigate factors influencing adherence to oral hygiene behaviors by elementary school children.DesignIn this cross‐sectional study, 988 elementary school children were chosen using the multistage cluster sampling method. Data were collected using the SCT scale, and its validity and reliability were confirmed. Theoretical models were examined using the structural equation modeling.ResultsThe SCT explained 50% of the variance in brushing with fluoridated toothpaste and 55.6% of the variance in flossing behaviors. The total effect of family environment (β = .60, P < .05), self‐efficacy in overcoming impediments (β = .50, P < .05), and emotional coping (β = .40, P < .05) variables in the conceptual model had significantly influenced tooth brushing behavior. The total effect of self‐efficacy (β = .79, P < .05), family environment (β = .41, P < .05), and situational perception (β = .35, P < .05) variables of the conceptual model significantly influenced the flossing behavior.ConclusionsThe SCT, self‐efficacy, and family environment were strongly associated with brushing and flossing behaviors. Therefore, supportive family environments should be considered as one of the top contributors to successful oral health promotion.
Predicting the flexural strength of Li‐ion‐conducting garnet type oxide for solid‐state‐batteries
Authors: Fu Zhezhen , McOwen Dennis , Zhang Lei , Gong Yunhui , Ren Yaoyu , Gritton J. Evans , Godbey Griffin , Dai Jiaqi , Hu Liangbing , Wachsman Eric 
Published: April 2020

AbstractThe mechanical strength of solid‐state electrolytes is crucial for applications in solid‐state batteries (eg block lithium dendrites and withhold the stress due to volume expansion of the electrode). We determined the flexural strength of doped Li7La3Zr2O12 (Li7La2.75Ca0.25Zr1.75Nb0.25O12, LLCZN) garnet type electrolyte as ~8.6 ± 1.5 MPa to ~51.5 ± 4.8 MPa as functions of porosity and grain size. Based on the experimental results, a series of theoretical models were established to obtain empirical equations to study the effects of porosity and grain size. Our further experiments demonstrate that the empirical equations can be used to predict the flexural strength of garnet type oxides based on its microstructure (porosity and grain size). Optimization of the grain size of fully dense garnet oxide can increase the strength up to ~106.0 ± 11.6 MPa (tape casting‐sintering method with a grain size of ~2.8 µm).
Endogenous thrombopoietin promotes non‐small‐cell lung carcinoma cell proliferation and migration by regulating EGFR signalling
Authors: Zou Zifang , Fan Xiaoxi , Liu Yang , Sun Yanbin , Zhang Xin , Sun Guanghao , Li Xuehao , Xu Shun 
Published: April 2020

AbstractThrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non‐small‐cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P‐TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand‐induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF‐stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.
The effect of population density on growth and survival of a Neotropical annual killifish
Authors: García Daniel , Reichard Martin 
Published: April 2020

AbstractWe used a field experiment to test the effects of population density on the growth rate and survival of Austrolebias bellottii, a Neotropical annual killifish. Effects differed between the sexes: males at high densities achieved a smaller final size and experienced higher mortality while no such effects were observed in females. This sex‐specific effect could be an indirect consequence of mate competition.