bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive enhancement interventions for people with bipolar disorder: A systematic review of methodological quality, treatment approaches, and outcomes
Authors: Tsapekos Dimosthenis , Seccomandi Benedetta , Mantingh Tim , Cella Matteo , Wykes Til , Young Allan H. 
Published: October 2019

AbstractBackgroundPatients with bipolar disorder (BD) suffer from cognitive deficits across several domains. The association between cognitive performance and psychosocial functioning has led to the emergence of cognition as a treatment target.ObjectiveThis study reviews the existing literature on cognitive enhancement interventions for people with BD, focusing on different treatment approaches and methodological quality.MethodsWe conducted a systematic search following the PRISMA guidelines. Sample characteristics and main outcomes for each study and treatment characteristics for each approach were extracted. Study quality was assessed using the Clinical Trials Assessment Measure (CTAM) and Cochrane Collaboration's Risk of Bias tool by independent raters.ResultsEleven articles reporting data from seven original studies were identified encompassing 471 participants. Two treatment approaches were identified, cognitive and functional remediation. For controlled studies, methodological quality was modest (average CTAM score = 60.3), while the overall risk of bias was considered moderate. Beneficial effects on cognitive or functional outcomes were reported in the majority of studies (91%), but these findings were isolated and not replicated across studies. Key methodological limitations included small sample sizes, poor description of randomization process, high attrition rates, and participant exclusion from the analysis.ConclusionsFindings are promising but preliminary. Quality studies were few and mostly underpowered. Heterogeneity in sample characteristics, outcome measures, and treatment approaches further limit the ability to generalize findings. Adequately powered trials are required to replicate initial findings, while moderators of treatment response and mechanisms of transfer need to be explored.
Molecular heterogeneity unravelled by single‐cell transcriptomics in patients with essential thrombocythaemia
Authors: Hsu Chia‐Chen , Chen Ying‐Ju , Huang Cih‐En , Wu Yu‐Ying , Wang Ming‐Chung , Pei Sung‐Nan , Liao Chun‐Kai , Lu Chang‐Hsien , Chen Ping‐Tsung , Tsou Hsing‐Yi , Li Chian‐Pei , Chuang Wei‐Hsuan , Chuang Ching‐Kai , Yang Cheng‐Yu , Lai Yi‐Hua , Lin Yi‐Hsuan , Chen Chih‐Cheng 
Published: October 2019

SummarySignificant phenotypic heterogeneity exists in patients with all subtypes of myeloproliferative neoplasms (MPN), including essential thrombocythaemia (ET). Single‐cell RNA sequencing (scRNA‐Seq) holds the promise of unravelling the biology of MPN at an unprecedented level of resolution. Herein we employed this approach to dissect the transcriptomes in the CD34+ cells from the peripheral blood of seven previously untreated ET patients and one healthy adult. The mutational profiles in these patients were as follows: JAK2 V617F in two, CALR in three (one type I and two type II) and triple‐negative (TN) in two. Our results reveal substantial heterogeneity within this enrolled cohort of patients. Activation of JAK/STAT signalling was recognized in discrepant progenitor lineages among different samples. Significantly disparate molecular profiling was identified in the comparison between ET patients and the control, between patients with different driver mutations (JAK2 V617F and CALR exon 9 indel), and even between patients harbouring the same driver. Intra‐individual clonal diversity was also found in the CD34+ progenitor population of a patient, possibly indicating the presence of multiple clones in this case. Estimation of subpopulation size based on cellular immunophenotyping suggested differentiation bias in all analysed samples. Furthermore, combining the transcriptomic information with data from targeted sequencing enabled us to unravel key somatic mutations that are molecularly relevant. To conclude, we demonstrated that scRNA‐Seq extended our knowledge of clonal diversity and inter‐individual heterogeneity in patients with ET. The obtained information could potentially leapfrog our efforts in the elucidation of the pathogenesis of the disease.
Optimal portfolio choices using financial leverage
Authors: Laborda Ricardo , Olmo Jose 
Published: October 2019

AbstractThis paper investigates the role of leverage in determining the investor's optimal asset allocation over multiperiod investment horizons. To do this, we allow investors to lever their financial position by borrowing from credit markets. GMM methods are used to estimate and test the optimal portfolio weights and individual's optimal choice of financial leverage. These optimal choices are assumed to be parametric functions of a set of state variables describing the evolution of the economy. The empirical application of this methodology to a portfolio of cash, bonds and stocks reveals that a) financial leverage limits the reaction of investors to changes in the investment opportunity set; b) individuals increase leverage during recessions and deleverage in expansionary periods; c) optimal portfolio weights and financial leverage are negatively related to the degree of investor's risk aversion and positively related to the investment horizon.
Accuracy of digital impressions for implant‐supported complete‐arch prosthesis, using an auxiliary geometry part—An in vitro study
Authors: Iturrate Mikel , Eguiraun Harkaitz , Solaberrieta Eneko 
Published: October 2019

AbstractObjectivesThe aim of this study was to evaluate the accuracy of complete‐arch digital impressions for fabrication of an implant‐supported prosthesis in the edentulous maxilla using an auxiliary geometry part.Materials and methodsA replica of the upper jaw of an edentulous patient with four scannable impression copings was fabricated in stainless steel. This model was scanned with an industrial non‐contact 3D structured blue light 3D scanner, and the measurements of three reference distances were established as reference values. Subsequently, the model was scanned in two different scenarios (with or without an auxiliary geometry part put in place and fixed to the model) using three intraoral scanners. Measurements were taken with 3D inspection software, and a digital impression of the complete arch was built with mesh processing software by combining 2 STL files obtained with an intraoral scanner.ResultsAll measurements with the auxiliary geometry part gave significantly more accurate results (p < .05). Trueness improved in the three reference distances, reaching values of 8 ± 6 µm at D12 reference distance, 20 ± 11 µm at D13 and 35 ± 22 µm at D14. Precision also improved significantly with the use of the auxiliary geometry part placed on the model (p < .05). The best precision results at reference distances D13 and D14 were obtained with the True Definition Scanner.ConclusionsThe proposed methodology significantly improves the accuracy of complete‐arch digital impressions in edentulous patients obtained in vitro, regardless of which scanner is used.
Designing instruction for complex learning: 4C/ID in higher education
Authors: Frerejean Jimmy , van Merriënboer Jeroen J.G. , Kirschner Paul A. , Roex Ann , Aertgeerts Bert , Marcellis Marco 
Published: October 2019

AbstractObjectives‐based instructional design approaches break down tasks into specific learning objectives and prescribe that instructors should choose the optimal instructional method for teaching each respective objective until all objectives have been taught. This approach is appropriate for many tasks where there is little relation between the objectives, but less effective for teaching complex professional tasks that require the integration of knowledge, skills, and attitudes and the coordination of different skills. For the latter, a task‐centred approach that starts designing instruction from whole, real‐life tasks, is more appropriate. This article describes one task‐centred instructional design model, namely the Four‐Component Instructional Design (4C/ID) model and illustrates its application by reflecting on three educational programs in higher education designed with 4C/ID. The first case presents a design for a course that focuses on the development of mobile apps at the Amsterdam University of Applied Sciences in the Netherlands. The second case illustrates the integration of information problem‐solving skills at Iselinge University of Professional Teacher Education, a teacher training institute in the Netherlands. The third case is an example from general practice education at the KU Leuven, Belgium. Future developments and issues concerning the implementation of task‐centred educational programmes are discussed.
Characteristics of 698 patients with dissociative seizures: A UK multicenter study
Authors: Goldstein Laura H. , Robinson Emily J. , Reuber Markus , Chalder Trudie , Callaghan Hannah , Eastwood Carole , Landau Sabine , McCrone Paul , Medford Nick , Mellers John D. C. , Moore Michele , Mosweu Iris , Murray Joanna , Perdue Iain , Pilecka Izabela , Richardson Mark P. , Carson Alan , Stone Jon ,   on behalf of the CODES Study Group
Published: October 2019

AbstractObjectiveWe aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology.MethodsWe collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations.ResultsIn what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed.SignificanceFemales with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.
Ultra‐long‐term subcutaneous home monitoring of epilepsy—490 days of EEG from nine patients
Authors: Weisdorf Sigge , Duun‐Henriksen Jonas , Kjeldsen Marianne J. , Poulsen Frantz R. , Gangstad Sirin W. , Kjær Troels W. 
Published: October 2019

AbstractObjectiveTo explore the feasibility of home monitoring of epilepsy patients with a novel subcutaneous electroencephalography (EEG) device, including clinical implications, safety, and compliance via the first real‐life test.MethodsWe implanted a beta‐version of the 24/7 EEG SubQ (UNEEG Medical A/S, Denmark) subcutaneously in nine participants with temporal lobe epilepsy. Data on seizures, adverse events, compliance in using the device, and use of antiepileptic drugs (AEDs) were collected. EEG was recorded for up to 3 months, and all EEG data were reviewed visually to identify electrographic seizures. These were descriptively compared to seizure counts and AED changes reported in diaries from the same period.ResultsFour hundred ninety days of EEG and 338 electrographic seizures were collected. Eight participants completed at least 9 weeks of home monitoring, while one cancelled participation after 4 weeks due to postimplantation soreness. In total, 13 cases of device‐related adverse events were registered, none of them serious. Recordings obtained from the device covered 73% of the time, on average (range 45%‐91%). Descriptively, electrographic seizure counts were substantially different from diary seizure counts. We uncovered several cases of underreporting and revealed important information on AED response. Electrographic seizure counts revealed circadian distributions of seizures not visible from seizure diaries.SignificanceThe study shows that home monitoring for up to 3 months with a subcutaneous EEG device is feasible and well tolerated. No serious adverse device‐related events were reported. An objective seizure count can be derived, which often differs substantially from self‐reported seizure counts. Larger clinical trials quantifying the benefits of objective seizure counting should be a priority for future research as well as development of algorithms for automated review of data.
The Practice of Family Life Education Within Early Head Start Home Visiting
Authors: Walsh Bridget A. , Mortensen Jennifer A. , Edwards Adrienne L. , Cassidy Dawn 
Published: October 2019

ObjectiveTo investigate relevant professionals' perspectives about potential collaboration between family life education (FLE) and home visiting in Early Head Start's Home‐Based Option (EHS‐HBO) to understand the merits and challenges of this partnership.BackgroundPractices for EHS‐HBO programs vary, which prevents the development of a consistent, evidence‐based home visiting model. Alignment with the strengths‐based family life education methodology (prevention, education, collaboration) may bring more consistency to EHS home visiting.MethodA purposive sample of 123 family life education, family science, and early childhood professionals completed a topical, open‐ended survey. Responses were analyzed by using qualitative content analysis.ResultsSeveral themes emerged from the data concerning (a) agreement that FLE is a viable approach to EHS‐HBO (e.g., the FLE approach is beneficial, includes relevant training, and professionalizes home visiting); and (b) potential obstacles in merging FLE and EHS‐HBO (e.g., deficiencies in FLE training for home visitors, certification requirements are restrictive, and lack of credential recognition).ConclusionFLE is a viable approach to EHS‐HBO, and programs approved by the National Council on Family relations provide valuable training for future home visitors. Participants expressed positive attitudes as well as insight about the interface of FLE and EHS home visiting.ImplicationsA current FLE approach to EHS‐HBO needs to be conceptualized and described more thoroughly, and a measure of home‐visitor fidelity to FLE should be developed. Research and alignment efforts are warranted on the synergy between FLE and EHS home visiting, which currently shows promise.
Structural and thermodynamic correlation illuminates the selective transport mechanism of disaccharide α‐glycosides through ABC transporter
Authors: Chandravanshi Monika , Gogoi Prerana , Kanaujia Shankar Prasad 
Published: October 2019

Carbohydrate (or sugar) molecules are extremely diverse regarding their length, linkage and epimeric state. Selective acquisition of these molecules inside the cell is achieved by the substrate (or solute)‐binding protein of ATP‐binding cassette (ABC) transport system. However, the molecular mechanism underlying the selective transport of diverse carbohydrates remains unclear mainly owing to their structural complexity and stereochemistry. This study reports crystal structures of an α‐glycoside‐binding protein (αGlyBP, ORF ID: TTHA0356 from Thermus thermophilus HB8) in complex with disaccharide α‐glycosides namely trehalose (α‐1,1), sucrose (α‐1,2), maltose (α‐1,4), palatinose (α‐1,6) and glucose within a resolution range of 1.6–2.0 Å. Despite transporting multiple types of sugars, αGlyBP maintains its stereoselectivity for both glycosidic linkage as well as an epimeric hydroxyl group. Out of the two subsites identified in the active‐site pocket, subsite B which accommodates the glucose and glycosyl unit of disaccharide α‐glycosides is highly conserved. In addition, structural data confirms the paradoxical behavior of glucose, where it replaces the high‐affinity ligand(s) (disaccharide α‐glycosides) from the active site of the protein. Comparative assessment of open and closed conformations of αGlyBP along with mutagenic and thermodynamic studies identifies the hinge region as the first interaction site for the ligands. On the other hand, encapsulation of ligand inside the active site is achieved through the N‐terminal domain (NTD) movement, whereas the C‐terminal domain (CTD) of αGlyBP is identified to be rigid and postulated to be responsible for maintaining the interaction with the transmembrane domain (TMD) during substrate translocation.DatabaseStructural data are available in RCSB Protein Data Bank under the accession number(s) 6J9W, 6J9Y, 6JAD, 6JAG, 6JAH, 6JAI, 6JAL, 6JAM, 6JAN, 6JAO, 6JAP, 6JAQ, 6JAR, 6JAZ, 6JB0, 6JB4, 6JBA, 6JBB and 6JBE.
Plant growth regulator and soil fertilizer improve production and growing stage of Brachiaria decumbens
Authors: Rocha Leone Campos , Teixeira Fábio Andrade , Pedreira Márcio dos Santos , Fries Daniela Deitos , Dias Daniel Lucas Santos , Costa Evely Giovanna Leite , de Figueiredo Abdias José , Seixas Angel Amaral , Pacheco Camile Carvalho , Santiago Bismarck Moreira 
Published: October 2019

AbstractIt is necessary to increase the rates of initial growth of pastures for use during the better planting period. Thus, two experiments were used to evaluate the effect of plant growth regulator (PGR; auxins, gibberellins and cytokinins) in seeds types (coated with polymer coating fungicide and conventional method) and nitrogen fertilization methods in Brachiaria decumbens cv. Basilisk on the germination, growth, development and physiological composition. From the regression estimates, lower levels of PGR (10.3; 12.8; 8.85 and 9.57 ml/kg for germination percentage, germination speed index, leaf and pseudostem, respectively) were recommended in coated seeds when compared to conventional method (untreated seeds, with polymer coating and fungicide). Leaf and pseudostem mass production had a significant interaction effect between seed type and the use of growth regulator. Coated seeds (with fungicide and polymers after scarification) had greater performance with absence or at lower levels (8.85 and 9.57 ml/kg seed) of growth regulators. This was not observed for conventional seeds, the higher doses (15.5 and 18.1 ml/kg) presented higher development for the same characteristics. In second experiment, rates of photoassimilate were increased by soil fertilization and use of PGRs. No influence of foliar fertilization was observed when used exclusively, but N‐fertilization multiple and soil promotes an increase in chlorophyll content and mass yield, respectively. The use of exogenous hormonal compounds acts on the organogenesis of plant tissues and increases the formation of plant tissues and acts in the promotion of germination and development of structures, making it a key tool in pasture establishment.
AMPK activity is required for the induction of anhydrobiosis in a tardigrade Hypsibius exemplaris, and its potential up‐regulator is PP2A
Authors: Kondo Koyuki , Mori Masaru , Tomita Masaru , Arakawa Kazuharu 
Published: October 2019

AbstractThe anhydrobiotic tardigrade, Hypsibius exemplaris, was previously considered to require de novo gene expression and protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activity for successful anhydrobiosis. These indicate that H. exemplaris has signal transduction systems responding to desiccation stress, with the involvement of phosphorylation events. To this end, we carried out time‐series phosphoproteomics of H. exemplaris exposed to mild desiccation stress and detected 48 phosphoproteins with significant differential regulations. Among them, immediate and successive reduction of phosphorylation levels of AMP‐activated protein kinase (AMPK) was observed. The subsequent chemical genetic approach showed that AMPK was activated during the preconditioning stage for anhydrobiosis, and inhibition of its activity impaired successful anhydrobiosis. As PP2A is known to dephosphorylate AMPK in other organisms, we suggested that decreased phosphorylation levels of AMPK upon mild desiccation stress were caused by dephosphorylation by PP2A. Accordingly, phosphoproteomics of animals pre‐treated with the PP1/PP2A inhibitor cantharidic acid (CA) lacked the decrease in phosphorylation levels of AMPK. These observations suggest that AMPK activity is required for successful anhydrobiosis in H. exemplaris, and its phosphorylation state is possibly regulated by PP2A.
Measurement of plasma and platelet tissue factor pathway inhibitor, factor V and Protein S in people with haemophilia
Authors: Ellery Paul E. R. , Hilden Ida , Thyregod Peter , Martinez Nicholas D. , Maroney Susan A. , Gill Joan C. , Mast Alan E. 
Published: October 2019

AbstractIntroductionTissue factor pathway inhibitor (TFPI) is a naturally occurring anticoagulant found in plasma, where it circulates bound to lipoproteins, factor V (FV) or Protein S (PS), and in platelets. Therapeutic agents targeting TFPI are under development for the treatment of haemophilia A and haemophilia B.AimTo begin to understand how TFPI, FV and PS interact to modulate haemophilia bleeding.MethodsPlasma and platelet antigen concentrations of these factors were determined in 73 people with haemophilia A and 18 with haemophilia B. Using multiple regression models, these were compared to the same analytes measured in 224 male blood donors.ResultsThere were no differences in plasma or platelet TFPI, FV or PS concentrations between haemophilia types or severities. However, compared to blood donors, people with haemophilia had approximately one‐third lower plasma PS, 9% lower plasma TFPIα, 50% higher platelet FV and 26% lower platelet Protein S.ConclusionTogether, the presented data suggest that individuals with haemophilia may have a compensatory procoagulant response of both plasma and platelet proteins to the decreased concentrations of FVIII or FIX.