bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Biologic Therapy on the Small Airways Asthma Phenotype
Authors: Chan Rory , Lipworth Brian J. 
Published: October 2022

AbstractThe small airways dysfunction (SAD) asthma phenotype is characterised by narrowing of airways < 2 mm in diameter between generations 8 and 23 of the bronchial tree. Recently, this has become particularly relevant as measurements of small airways using airway oscillometry for example, are strong determinants of asthma control and exacerbations in moderate-to-severe asthma. The small airways can be assessed using spirometry as forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25–75) and has been deemed more accurate in detecting small airways dysfunction than forced expiratory volume in 1 s (FEV1). Oscillometry as the heterogeneity in resistance between 5 and 20 Hz (R5–R20), low frequency reactance at 5 Hz (X5) or area under the reactance curve between 5 Hz and the resonant frequency can also be used to assess the small airways. The small airways can also be assessed using the multiple breath nitrogen washout (MBNW) test giving rise to values including functional residual capacity, lung clearance index and ventilation distribution heterogeneity in the conducting (Scond) and the acinar (Sacin) airways. The ATLANTIS group showed that the prevalence of small airways disease in asthma defined on FEF25–75, oscillometry and MBNW all increased with progressive GINA asthma disease stages. As opposed to topical inhaler therapy that might not adequately penetrate the small airways, it is perhaps more intuitive that systemic anti-inflammatory therapy with biologics targeting downstream cytokines and upstream epithelial anti–alarmins may offer a promising solution to SAD. Here we therefore aim to appraise the available evidence for the effect of anti-IgE, anti-IL5 (Rα), anti-IL4Rα, anti-TSLP and anti-IL33 biologics on small airways disease in patients with severe asthma.
Processing of sensory, painful and vestibular stimuli in the thalamus
Authors: Habig Kathrin , Krämer Heidrun H. , Lautenschläger Gothje , Walter Bertram , Best Christoph 
Published: October 2022

Abstract
Objectives
The thalamus plays an important role in the mediation and integration of various stimuli (e.g., somatosensory, pain, and vestibular). Whether a stimulus-specific and topographic organization of the thalamic nuclei exists is still unknown. The aim of our study was to define a functional, in vivo map of multimodal sensory processing within the human thalamus.

Methods
Twenty healthy individuals (10 women, 21–34 years old) participated. Defined sensory stimuli were applied to both hands (innocuous touch, mechanical pain, and heat pain) and the vestibular organ (galvanic stimulation) during 3 T functional MRI.

Results
Bilateral thalamic activations could be detected for touch, mechanical pain, and vestibular stimulation within the left medio-dorsal and right anterior thalamus. Heat pain did not lead to thalamic activation at all. Stimuli applied to the left body side resulted in stronger activation patterns. Comparing an early with a late stimulation interval, the mentioned activation patterns were far more pronounced within the early stimulation interval.

Conclusions
The right anterior and ventral-anterior nucleus and the left medio-dorsal nucleus appear to be important for the processing of multimodal sensory information. In addition, galvanic stimulation is processed more laterally compared to mechanical pain. The observed changes in activity within the thalamic nuclei depending on the stimulation interval suggest that the stimuli are processed in a thalamic network rather than a distinct nucleus. In particular, the vestibular network within the thalamus recruits bilateral nuclei, rendering the thalamus an important integrative structure for vestibular function.
Using virtual reality to train infection prevention: what predicts performance and behavioral intention?
Authors: Désiron J. C. , Petko D. , Lapaire V. , Ullrich C. , Clack L. 
Published: October 2022

AbstractTraining medical professionals for hand hygiene is challenging, especially due to the invisibility of microorganisms to the human eye. As the use of virtual reality (VR) in medical training is still novel, this exploratory study investigated how preexisting technology acceptance and in-training engagement predict VR hand hygiene performance scores. The effect of training in the VR environment on the behavioral intention to further use this type of training device (a component of technology acceptance) was also investigated. Participants completed a VR hand hygiene training comprising three levels of the same task with increasing difficulty. We measured technology acceptance, composed of performance expectancy, effort expectancy, and behavioral intention, pre- and post-training, and in-training engagement using adaptations of existing questionnaires. We used linear regression models to determine predictors of performance in level-3 and of behavioral intention to further use VR training. Forty-three medical students participated in this exploratory study. In-training performance significantly increased between level-1 and level-3. Performance in level-3 was predicted by prior performance expectancy and engagement during the training session. Intention to further use VR to learn medical procedures was predicted by both prior effort expectancy and engagement. Our results provide clarification on the relationship between VR training, engagement, and technology acceptance. Future research should assess the long-term effectiveness of hand hygiene VR training and the transferability of VR training to actual patient care in natural settings. A more complete VR training could also be developed, with additional levels including more increased difficulty and additional medical tasks.
The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options
Authors: Wang Yating , Tang Shou-Ching 
Published: October 2022

AbstractHormonal therapy plays a vital part in the treatment of estrogen receptor–positive (ER +) breast cancer. ER can be activated in a ligand-dependent and independent manner. Currently available ER-targeting agents include selective estrogen receptor modulators (SERMs), selective estrogen receptor degraders (SERDs), and aromatase inhibitors (AIs). Estrogen receptor mutation (ESR1 mutation) is one of the common mechanisms by which breast cancer becomes resistant to additional therapies from SERMs or AIs. These tumors remain sensitive to SERDs such as fulvestrant. Fulvestrant is limited in clinical utilization by its intramuscular formulation and once-monthly injection in large volumes. Oral SERDs are being rapidly developed to replace fulvestrant with the potential of higher efficacy and lower toxicities. Elacestrant is the first oral SERD that went through a randomized phase III trial showing increased efficacy, especially in tumors bearing ESR1 mutation, and good tolerability. Two other oral SERDs recently failed to achieve the primary endpoints of longer progression-free survival (PFS). They targeted tumors previously treated with several lines of prior therapies untested for ESR1 mutation. Initial clinical trial data demonstrated that tumors without the ESR1 mutation are less likely to benefit from the SERDs and may still respond to SERMs or AIs, including tumors previously exposed to hormonal therapy. Testing for ESR1 mutation in ongoing clinical trials and in hormonal therapy for breast cancer is highly recommended. Novel protein degradation technologies such as proteolysis-targeting chimera (PROTACS), molecular glue degrader (MGD), and lysosome-targeting chimeras (LYTACS) may result in more efficient ER degradation, while ribonuclease-targeting chimeras (RIBOTAC) and small interfering RNA (siRNA) may inhibit the production of ER protein.
Nanoparticle release from anionic nanocellulose hydrogel matrix
Authors: Auvinen Vili-Veli , Laurén Patrick , Shen Boxuan , Isokuortti Jussi , Durandin Nikita , Lajunen Tatu , Linko Veikko , Laaksonen Timo 
Published: October 2022

AbstractNanocellulose hydrogels have been shown to be excellent platforms for sustained delivery of drug molecules. In this study, we examine the suitability of anionic nanocellulose hydrogels for the sustained release of various nanoparticles. Systems releasing nanoparticles could produce applications especially for therapeutic nanocarriers, whose life-times in vivo might be limited. Micelles, liposomes and DNA origami nanostructures were incorporated into the nanocellulose hydrogels, and their release rates were measured. Two different hydrogel qualities (with 1% and 2% mass of fiber content) were used for each nanoparticle formulation. We showed that the drug release rates depend on nanoparticle size, shape, and charge. Smaller particles with neutral charge were released faster from 1% hydrogels than from 2% hydrogels. Nanoparticles with cationic labeling were retained in both hydrogels, whereas for the neutral nanoparticles, we were able to determine the cut-off size for released particles for both hydrogels. Rod-shaped DNA origami were released rapidly even though their length was above the cut-off size of spherical particles, indicating that their smaller radial dimension facilitates their fast release. Based on our results, anionic nanocellulose hydrogels are versatile platforms for the sustained release of the chosen model nanoparticles (liposomes, micelles, and DNA origami). Alternatively, for the tightly bound nanoparticles, this could lead to nanoparticle reservoirs within hydrogels, which could act as immobilized drug release systems.
Students’ continuance intention to use MOOCs: empirical evidence from India
Authors: Rekha I S , Shetty Jyothi , Basri Savitha 
Published: October 2022

AbstractIn recent years, there has been an increasing interest in understanding the Massive open online courses (MOOCs) due to its gaining popularity. Even though the number of online platforms and programs has grown during the COVID-19 pandemic, there is still a high rate of dropout and non-completion. In this work, the expectation-confirmation model is combined with MOOC features such as perceived openness, perceived reputation, and other factors i.e., perceived enjoyment, and perceived computer self-efficacy to investigate the learner’s continued intention to use MOOC. A survey was undertaken and the data was collected from 383 students pursuing their degrees (undergraduate and post-graduate) in Karnataka state, India. The collected data were analyzed with structural equation modelling in Smart PLS 3. The study confirms a significant influence of confirmation and perceived usefulness on satisfaction, and direct significant influence of perceived computer self-efficacy, satisfaction, and perceived usefulness on continuance intention. Also, the results demonstrated the significant influence of confirmation on perceived enjoyment and usefulness and the effect of computer self-efficacy on usefulness. The findings in this study indicate that the MOOC platforms should focus on confirming learner expectations and the usefulness of courses to ensure student satisfaction and continuance of courses.
Emergentist Integrated Information Theory
Authors: Negro Niccolò 
Published: October 2022

AbstractThe integrated information theory (IIT) is an ambitious theory of consciousness that aims to provide both a neuroscientific and a metaphysical account of consciousness by identifying consciousness with integrated information. In the philosophical literature, IIT is often associated with a panpsychist worldview. In this paper, I show that IIT can be considered, instead, as a form of emergentism that is incompatible with panpsychism. First, I show that the panpsychist interpretation of IIT is based on two properties of integrated information: intrinsicality and fundamentality. I show that the way IIT deals with these two properties, however, aligns better with emergentism than panpsychism. Then, after plugging some anti-panpsychist assumptions into IIT’s structure, I analyse different philosophical options for interpreting the formal result of causal emergence of integrated information in terms of dependence on and autonomy from its physical substrate. The upshot is that integrated information can be seen as dependent upon the fusion of the cause-effect powers of a physical substrate, and as autonomous in virtue of global-to-local determination. According to this interpretation, consciousness is the constraining power of the system as a whole upon itself, when this power emerges from the fusion on the cause-effect powers of the system’s components.
A NOTE ON FREQUENT HYPERCYCLICITY OF OPERATORS THAT $$\lambda$$-COMMUTE WITH THE DIFFERENTIATION OPERATOR
Authors: León-Saavedra Fernando , de la Rosa María Pilar Romero 
Published: October 2022

AbstractA continuous linear operator on a Fréchet space $$\mathcal {X}$$
X
is frequently hypercyclic if there exists a vector x such that for any nonempty open subset $$U\subset \mathcal {X}$$

U
⊂
X

the set of $$n\in \mathbb {N}\cup \{0\}$$

n
∈
N
∪
{
0
}

for which $$T^nx\in U$$

T
n

x
∈
U

has a positive lower density. Here we determine when an operator that commutes up to a factor with the differentiation operator D, defined on the space of entire functions, is frequently hypercyclic.
Hitting the target: stopping active learning at the cost-based optimum
Authors: Pullar-Strecker Zac , Dost Katharina , Frank Eibe , Wicker Jörg 
Published: October 2022

AbstractActive learning allows machine learning models to be trained using fewer labels while retaining similar performance to traditional supervised learning. An active learner selects the most informative data points, requests their labels, and retrains itself. While this approach is promising, it raises the question of how to determine when the model is ‘good enough’ without the additional labels required for traditional evaluation. Previously, different stopping criteria have been proposed aiming to identify the optimal stopping point. Yet, optimality can only be expressed as a domain-dependent trade-off between accuracy and the number of labels, and no criterion is superior in all applications. As a further complication, a comparison of criteria for a particular real-world application would require practitioners to collect additional labelled data they are aiming to avoid by using active learning in the first place. This work enables practitioners to employ active learning by providing actionable recommendations for which stopping criteria are best for a given real-world scenario. We contribute the first large-scale comparison of stopping criteria for pool-based active learning, using a cost measure to quantify the accuracy/label trade-off, public implementations of all stopping criteria we evaluate, and an open-source framework for evaluating stopping criteria. Our research enables practitioners to substantially reduce labelling costs by utilizing the stopping criterion which best suits their domain.
Sequencing and de novo assembly of the Koshihikari genome and identification of the genomic region related to the eating quality of cooked rice
Authors: Lee Yoon Kyung , Lee Yunjoo , Jang Su , Lee Taeyoung , Woo Mi-Ok , Seo Jeonghwan , Kim Backki , Koh Hee-Jong 
Published: October 2022

AbstractThe japonica rice (Oryza sativa L.) cultivar Koshihikari is considered an important breeding material with good eating quality (EQ). To effectively utilize Koshihikari in molecular breeding programs, determining its whole genome sequence including cultivar-specific segment is crucial. Here, the Koshihikari genome was sequenced using Nanopore and Illumina platforms, and de novo assembly was performed. A highly contiguous Koshihikari genome sequence was compared with Nipponbare, the reference genome of japonica. Genome-wide synteny was observed, as expected, without large structural variations. However, several gaps in alignment were detected on chromosomes 3, 4, 9, and 11. It was notable that previously identified EQ-related QTLs were found in these gaps. Moreover, sequence variations were identified in chromosome 11 at a region flanking the P5 marker, one of the significant markers of good EQ. The Koshihikari-specific P5 region was found to be transmitted through the lineage. High EQ cultivars derived from Koshihikari possessed P5 sequences; on the other hand, Koshihikari-derived low EQ cultivars didn’t contain the P5 region, which implies that the P5 genomic region affects the EQ of Koshihikari progenies. The EQ of near-isogenic lines (NILs) of Samnam (a low EQ cultivar) genetic background harboring the P5 segment was improved compared to that of Samnam in Toyo taste value. The structure of the Koshihikari-specific P5 genomic region associated with good EQ was analyzed, which is expected to facilitate the molecular breeding of rice cultivars with superior EQ.
Designing narrative for professional development: A programme for improving international health care practitioners’ cultural competence
Authors: Short Alison 
Published: October 2022

AbstractTo maintain and improve skills for practice, health care professionals across all disciplines need to engage in ongoing professional development. However, helping clinicians learn and apply new knowledge in practice can be challenging. This article reports on a purpose-designed professional development programme targeting experienced practitioners of a particular music therapy, focusing on their cultural competency. The author conceptualised a workshop format with a relevant clinical scenario at its centre. She describes how she developed the programme, which she subsequently delivered to an international community of 57 practitioners attending professional development conferences. To capture participants’ reactions and evidence of their new thinking applied to an everyday clinical practice, she used Brookfield’s Critical Incident Questionnaire (CIQ). Her analysis of the data, which provided feedback on the training scenario and structured group discussion materials, found that this continuing professional development training workshop was effective in challenging clinicians to think differently, and to plan the application of their newly acquired knowledge to their everyday practice. This paradigmatic case study contributes new knowledge towards the current reform of health systems, where achieving person-centred health care depends on the ongoing professional development of established health practitioners. Replacing traditional health care, where the patient receiving treatment is accorded a passive role, person-centred health care engages patients’ active participation in their therapy. Practitioners who have graduated a while ago therefore need to change some of their ingrained practices and approaches in treating their clients and patients, which will then lead to improved health outcomes.
An Agrobacterium strain auxotrophic for methionine is useful for switchgrass transformation
Authors: Prías-Blanco Mónica , Chappell Timothy M. , Freed Emily F. , Illa-Berenguer Eudald , Eckert Carrie A. , Parrott Wayne A. 
Published: October 2022

AbstractAuxotrophic strains of Agrobacterium tumefaciens can contribute to the development of more efficient transformation systems, especially for crops historically considered recalcitrant. Homologous recombination was used to derive methionine auxotrophs of two common A. tumefaciens strains, LBA4404 and EHA105. The EHA105 strains were more efficient for switchgrass transformation, while both the EHA105 and LBA4404 strains worked equally well for the rice control. Event quality, as measured by transgene copy number, was not affected by auxotrophy, but was higher for the LBA4404 strains than the EHA105 strains. Ultimately, the use of auxotrophs reduced bacterial overgrowth during co-cultivation and decreased the need for antibiotics.
Global Sensitivity Analysis of a Coupled Hydro-Economic Model and Groundwater Restriction Assessment
Authors: Rodríguez-Flores José M. , Valero Fandiño Jorge A. , Cole Spencer A. , Malek Keyvan , Karimi Tina , Zeff Harrison B. , Reed Patrick M. , Escriva-Bou Alvar , Medellín-Azuara Josué 
Published: October 2022

AbstractAssessing impacts on coupled food-water systems that may emerge from water policies, changes in economic drivers and crop productivity requires an understanding of dominant uncertainties. This paper assesses how a candidate groundwater pumping restriction and crop prices, crop yields, surface water price, electricity price, and parametric uncertainties shape economic and groundwater performance metrics from a coupled hydro-economic model (HEM) through a diagnostic global sensitivity analysis (GSA). The HEM used in this study integrates a groundwater depth response, modeled by an Artificial Neural Network (ANN), into a calibrated Positive Mathematical Programming (PMP) agricultural production model. Results show that in addition to a groundwater pumping restriction, performance metrics are highly sensitive to prices and yields of perennial tree crops. These sensitivities become salient during dry years when there is a higher reliance on groundwater. Furthermore, results indicate that performing a GSA for two different water baseline conditions used to calibrate the production model, dry and wet, result in different sensitivity indices magnitudes and factor prioritization. Diagnostic GSA results are used to understand key factors that affect the performance of a groundwater pumping restriction policy. This research is applied to the Wheeler Ridge-Maricopa Water Storage District located in Kern County, California, region reliant on groundwater and vulnerable to surface water shortages.
NMR-based metabolic profiling of children with premature adrenarche
Authors: Matzarapi Konstantina , Giannakopoulos Aristeidis , Chasapi Styliani A. , Kritikou Dimitra , Efthymiadou Alexandra , Chrysis Dionisios , Spyroulias Georgios A. 
Published: October 2022

Abstract
Introduction
Premature adrenarche (PA) for long time was considered a benign condition but later has been connected to various diseases in childhood and adulthood which remains controversial.

Objective
To investigate the effect of premature adrenarche on the metabolic phenotype, and correlate the clinical and biochemical data with the metabolic profile of children with PA.

Methods
Nuclear magnetic resonance (NMR)-based untargeted and targeted metabolomic approach in combination with multivariate and univariate statistical analysis applied to study the metabolic profiles of children with PA. Plasma, serum, and urine samples were collected from fifty-two children with Idiopathic PA and forty-eight age-matched controls from the division of Pediatric Endocrinology of the University Hospital of Patras were enrolled.

Results
Metabolomic results showed that plasma and serum glucose, myo-inositol, amino acids, a population of unsaturated lipids, and esterified cholesterol were higher and significantly different in PA children. In the metabolic profiles of children with PA and age-matched control group a gradual increase of glucose and myo-inositol levels was observed in serum and plasma, which was positively correlated their body mass index standard deviation score (BMI SDS) values respectively. Urine 1H NMR metabolic fingerprint of PA children showed positive correlation and a clustering-dependent relationship with their BMI and bone age (BA) respectively.

Conclusion
This study provides evidence that PA driven metabolic changes begin during the childhood and PA may has an inductive role in a BMI–driven increase of specific metabolites. Finally, urine may be considered as the best biofluid for identification of the PA metabolism as it reflects more clearly the PA metabolic fingerprint.