bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applicability of the DPRA on mixture testing: challenges and opportunities
Authors: Marcelis Quinten , Deconinck Eric , Rogiers Vera , Vanhaecke Tamara , Desmedt Bart 
Published: July 2023

AbstractThe in chemico direct peptide reactivity assay (DPRA) is validated to assess protein reactivity of chemical compounds, relating to the molecular initiating event of skin sensitization induction. According to OECD TG 442C, the DPRA is technically applicable to test multi-constituent substances and mixtures of known composition, even though limited experimental data are publicly available. First, we assessed the DPRA’s predictive capability for individual substances, but at concentrations other than the recommended 100 mM, i.e., based on the LLNA EC3 concentration (Experiment A). Next, the applicability of the DPRA to test unknown mixtures was assessed (Experiment B). Here, the complexity of unknown mixtures was reduced to mixtures containing either two known skin sensitizers with varying potencies, or a combination of a skin sensitizer with a non-skin sensitizer, or multiple non-sensitizers. Experiments A and B revealed that one extremely potent sensitizer (oxazolone) was incorrectly classified as a non-sensitizer when tested at its low EC3 concentration of 0.4 mM instead of the suggested molar excess conditions of 100 mM (Experiments A). For binary mixtures tested in experiments B, the DPRA was able to distinguish all skin sensitizers and the strongest skin sensitizer in the mixture was determinant for the overall peptide depletion of a sensitizer. In conclusion, we confirmed that the DPRA test method can be used efficiently for well-known characterized mixtures. However, when deviating from the recommended testing concentration of 100 mM, caution should be taken in case of negative results, limiting the DPRA’s applicability for mixtures of unknown composition.
Proton pump inhibitor use: systematic review of global trends and practices
Authors: Shanika Lelwala Guruge Thushani , Reynolds Andrew , Pattison Sharon , Braund Rhiannon 
Published: July 2023

Abstract
Purpose
Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in the short-term, emerging evidence shows risks associated with long-term use. Current evidence on global PPI use is scarce. This systematic review aims to evaluate global PPI use in the general population.

Methods
Ovid MEDLINE, Embase, and International Pharmaceutical Abstracts were systematically searched from inception to 31 March 2023 to identify observational studies on oral PPI use among individuals aged ≥ 18 years. PPI use was classified by demographics and medication factors (dose, duration, and PPI types). The absolute numbers of PPI users for each subcategory were summed and expressed as a percentage.

Results
The search identified data from 28 million PPI users in 23 countries from 65 articles. This review indicated that nearly one-quarter of adults use a PPI. Of those using PPIs, 63% were less than 65 years. 56% of PPI users were female, and “White” ethnicities accounted for 75% of users. Nearly two-thirds of users were on high doses (≥ defined daily dose (DDD)), 25% of users continued PPIs for > 1 year, and 28% of these continued for > 3 years.

Conclusion
Given the widespread use PPIs and increasing concern regarding long-term use, this review provides a catalyst to support more rational use, particularly with unnecessary prolonged continuation. Clinicians should review PPI prescriptions regularly and deprescribe when there is no appropriate ongoing indication or evidence of benefit to reduce health harm and treatment cost.
Retrospective rationalization of disparities between the concentration dependence of diffusion coefficients obtained by boundary spreading and dynamic light scattering
Authors: Winzor Donald J. , Dinu Vlad , Scott David J. , Harding Stephen E. 
Published: July 2023

AbstractThis study establishes the existence of substantial agreement between published results from traditional boundary spreading measurements (including synthetic boundary measurements in the analytical ultracenrifuge) on two globular proteins (bovine serum albumin, ovalbumin) and the concentration dependence of diffusion coefficient predicted for experiments conducted under the operative thermodynamic constraints of constant temperature and solvent chemical potential. Although slight negative concentration dependence of the translational diffusion coefficient is the experimentally observed as well as theoretically predicted, the extent of the concentration dependence is within the limits of experimental uncertainty inherent in diffusion coefficient measurement. Attention is then directed toward the ionic strength dependence of the concentration dependence coefficient ($${k}_{D}$$

k
D

) describing diffusion coefficients obtained by dynamic light scattering, where, in principle, the operative thermodynamic constraints of constant temperature and pressure preclude consideration of results in terms of single-solute theory. Nevertheless, good agreement between predicted and published experimental ionic strength dependencies of $${k}_{D}$$

k
D

for lysozyme and an immunoglobulin is observed by a minor adaptation of the theoretical treatment to accommodate the fact that thermodynamic activity is monitored on the molal concentration scale because of the constraint of constant pressure that pertains in dynamic light scattering experiments.
Left atrial conduction times and regional velocities in persistent atrial fibrillation patients with and without fibrotic atrial cardiomyopathy
Authors: Heil Emanuel , Gerds-Li Jin-Hong , Keznickl-Pulst Julian , Furundzija-Cabraja Vesna , Hohendanner Felix , Boldt Leif-Hendrik , Stawowy Philipp , Schoeppenthau Doreen 
Published: July 2023

AbstractDespite the progress in understanding left atrial substrate and arrhythmogenesis, only little is known about conduction characteristics in atrial fibrillation patients with various stages of fibrotic atrial cardiomyopathy (FACM). This study evaluates left atrial conduction times and conduction velocities based on high-density voltage and activation maps in sinus rhythm (CARTO®3 V7) of 53 patients with persistent atrial fibrillation (LVEF 60% (55–60 IQR), LAVI 39 ml/m2 (31–47 IQR), LApa 24 ± 6 cm2). Measurements were made in low voltage areas (LVA ≤ 0.5 mV) and normal voltage areas (NVA ≥ 1.5 mV) at the left atrial anterior and posterior walls. Maps of 28 FACM and 25 no FACM patients were analyzed (19 FACM I/II, 9 FACM III/IV, LVA 14 ± 11 cm2). Left atrial conduction time averaged to 110 ± 24 ms but was shown to be prolonged in FACM (119 ms, + 17%) when compared to no FACM patients (101 ms, p = 0.005). This finding was pronounced in high-grade FACM (III/IV) (133 ms, + 31.2%, p = 0.001). In addition, the LVA extension correlated significantly with the left atrial conduction time (r = 0.56, p = 0.002). Conduction velocities were overall slower in LVA than in NVA (0.6 ± 0.3 vs. 1.3 ± 0.5 m/s, -51%, p < 0.001). Anterior conduction appeared slower than posterior, which was significant in NVA (1 vs. 1.4 m/s, -29%, p < 0.001) but not in LVA (0.6 vs. 0.8 m/s, p = 0.096). FACM has a significant influence on left atrial conduction characteristics in patients with persistent atrial fibrillation. Left atrial conduction time prolongs with the grade of FACM and the quantitative expanse of LVA up to 31%. LVAs show a 51% conduction velocity reduction compared to NVA. Moreover, regional conduction velocity differences are present in the left atrium when comparing anterior to posterior walls. Our data may influence individualized ablation strategies.
Early fitting in cochlear implant surgery: preliminary results
Authors: Soncini Arianna , Franzini Sebastiano , Di Marco Francesca , Riccardi Pasquale , Bacciu Andrea , Pasanisi Enrico , Di Lella Filippo 
Published: July 2023

Abstract
Purpose
Cochlear implants are usually activated 3–5 weeks after surgery; to date, no universal protocol exists regarding switch on and fitting of these devices. The aim of the study was to assess safety and functional results of activation and fitting of cochlear implant within 24 h following surgery.

Methods
In this retrospective case–control study, 15 adult patients who underwent cochlear implant surgery, for a total of 20 cochlear implant procedures were analyzed. In particular, clinical safety and feasibility were investigated by examinating patients at activation and at each follow-up. Values of electrodes’ impedance and most comfortable loudness (MCL) were analyzed from the time of surgery to 12 months after activation. Free-field pure tone average (PTA) was also recorded.

Results
No major or minor complications were reported and all patients could perform the early fitting. Activation modality influenced impedance values only in the short term but the differences were not statistically significant (p > 0.05). Mean MCL values in the early fitting group were lower than MCL of the late fitting in all follow-up sessions, and the difference was statistically significant (p < 0.05). The mean PTA was lower in the early fitting group but the difference was not statistically significant (p < 0.05).

Conclusions
Early fitting of cochlear implants is safe, allows for an early rehabilitation and can have possible beneficial effects on stimulation levels and dynamic range.
The effects of water temperature on cerebral blood flow during aquatic exercise
Authors: Carter Howard H. , Pienaar Oliver , Coleman Alexander , Cheng Jem L. , MacDonald Maureen J. , Naylor Louise H. , Green Daniel J. 
Published: July 2023

Abstract
Purpose
Recent studies suggest that episodic increases in cerebral blood flow (CBF) may contribute to the improvement in brain health associated with exercise training. Optimising CBF during exercise may enhance this benefit. Water immersion in ~ 30–32 °C augments CBF at rest and during exercise; however, the impact of water temperature on the CBF response has not been investigated. We hypothesised that cycle ergometry in water would increase CBF compared to land-based exercise, and that warm water would attenuate the CBF benefits.

Methods
Eleven young heathy participants (nine males; 23.8 ± 3.1 yrs) completed 30 min of resistance-matched cycle exercise in three separate conditions; non-immersion (Land), 32 °C and 38 °C water immersion up to the level of the waist. Middle cerebral artery velocity (MCAv), blood pressure, and respiratory measures were assessed throughout the exercise bouts.

Results
Core temperature was significantly higher in the 38 °C immersion than 32 °C (+ 0.84 ± 0.24 vs + 0.04 ± 0.16, P < 0.001), whilst mean arterial pressure was lower during 38 °C exercise compared to Land (84 ± 8 vs 100 ± 14 mmHg, P < 0.001) and 32 °C (92 ± 9, P = 0.03). MCAv was higher in 32 °C immersion compared to the Land and 38 °C conditions throughout the exercise bout (68 ± 10 vs 64 ± 11 vs 62 ± 12 cm/s, P = 0.03 and P = 0.02, respectively).

Conclusion
Our findings suggest that cycle exercise in warm water attenuates the beneficial impact of water immersion on CBF velocity due to redistribution of blood flow to subserve thermoregulatory demand. Our findings suggest that, whilst water-based exercise can have beneficial effects on cerebrovascular function, water temperature is a key determinant of this benefit.
On evolutionary problems with a-priori bounded gradients
Authors: Bulíček Miroslav , Hruška David , Málek Josef 
Published: July 2023

AbstractWe study a nonlinear evolutionary partial differential equation that can be viewed as a generalization of the heat equation where the temperature gradient is a priori bounded but the heat flux provides merely $$L^1$$

L
1

-coercivity. Applying higher differentiability techniques in space and time, choosing a special weighted norm (equivalent to the Euclidean norm in $$\mathbb {R}^d$$

R

d

), incorporating finer properties of integrable functions and flux truncation techniques, we prove long-time and large-data existence and uniqueness of weak solution, with an $$L^1$$

L
1

-integrable flux, to an initial spatially-periodic problem for all values of a positive model parameter. If this parameter is smaller than $$2/(d+1)$$

2
/
(
d
+
1
)

, where d denotes the spatial dimension, we obtain higher integrability of the flux. As the developed approach is not restricted to a scalar equation, we also present an analogous result for nonlinear parabolic systems in which the nonlinearity, being the gradient of a strictly convex function, gives an a-priori $$L^\infty $$

L
∞

-bound on the gradient of the unknown solution.
Triaxial Deformation of the Goldwyer Gas Shale at In Situ Stress Conditions—Part II: Viscoelastic Creep/Relaxation and Frictional Failure
Authors: Mandal Partha Pratim , Sarout Joel , Rezaee Reza 
Published: July 2023

AbstractTo understand the geomechanical implications of long-term creep (time-dependent deformation) response of gas shale, short-duration creep was recorded from laboratory triaxial tests on ten Goldwyer gas shale samples in the onshore Canning Basin at in situ stress conditions under constant differential axial stress. A simple power-law function captures primary creep behaviour involving elastic compliance constant B and time-dependent factor n. Experimental creep data revealed larger axial creep strain in clay and organic-rich rocks, than those dominated by carbonates. Anisotropic nature of creep was observed depending upon the direction of constant axial stress application (perpendicular or parallel to the bedding plane). Upon the application of linear viscoelastic theory on laboratory creep fitting coefficients, differential horizontal stress accumulation over a geological time scale was estimated from the viscoelastic stress relaxation concept. Further, this model was used to derive lithology-dependent least principal stress (Shmin) magnitude at depth for two vertical wells intersecting the Goldwyer gas shale formations. This newly proposed Shmin model was found to have a profound influence on designing hydraulic fracture simulation. Further, pore size distribution and specific surface area value SN2 were derived from low-pressure gas adsorption experiments. These physical properties along with weak mineral components were linked with creep constitutive parameters to understand the physical mechanisms of creep. A strong correlation was noted between SN2 and creep parameters n and B. Finally, an attempt was made to investigate how gas shale composition and failure frictional properties can influence shear fracturing.
Impact of hemicelluloses and crystal size on X-ray scattering from atomistic models of cellulose microfibrils
Authors: Zitting Aleksi , Paajanen Antti , Penttilä Paavo A. 
Published: July 2023

AbstractX-ray scattering methods allow efficient characterization of cellulosic materials, but interpreting their results is challenging. By creating molecular dynamics models of cellulose microfibrils and calculating the scattering from them, we investigated how different properties of the structures affect their scattering intensities. We studied the effects of hemicelluloses and crystal size on small-angle and wide-angle X-ray scattering (SAXS, WAXS). Microfibril models with and without surface-bound hemicelluloses were built based on the chemical composition of spruce secondary cell walls. The effect of fibril size was investigated by comparing the scattering from fibrils with 14 to 40 cellulose chains. The hemicelluloses appeared in the SAXS region as an increase in the fibril radius and as a clear contribution of a shell around the fibril. The hemicelluloses also increased the crystal size as determined from the broadening of the 200 diffraction peak of cellulose $$\textrm{I}_\upbeta$$

I
β

. The SAXS and WAXS analysis provided consistent estimates for the size of the microfibrils, and their special features and challenges were discussed. In particular, the results of 18-chain microfibrils were consistent with prior experimental results. Carrying out the simulations in wet and dry environments had the most pronounced effect on fibrils with a hemicellulose coating. Twisting of the fibril had very little impact on most properties, except for a minor effect on the WAXS peaks. The results allow for more correct interpretation of experimental scattering results, leading to more accurate descriptions of microfibril structures in natural and processed cellulosic materials.
Between death and suffering: resolving the gamer’s dilemma
Authors: Coghlan Thomas , Cox Damian 
Published: July 2023

AbstractThe gamer’s dilemma, initially proposed by Luck (Ethics and Information Technology 11(1):31–36, 2009) posits a moral comparison between in-game acts of murder and in-game acts of paedophilia within single-player videogames. Despite each activity lacking the obvious harms of their real-world equivalents, common intuitions suggest an important difference between them. Some responses to the dilemma suggest that intuitive responses to the two cases are based on important differences between the acts themselves or their social meaning. Others challenge the fundamental assumptions of the dilemma. In this paper, we identify and explore key imaginative and emotional differences in how certain types of in-game violence are experienced by players, consider how these differences factor into the moral lives of players, and use these insights to resolve the dilemma. The view we develop is that the key moral emotion in offensive video gameplay is self-repugnance. This is not repugnance of the act one directs a game character to perform in the game, nor repugnance of the character one plays. It is repugnance of oneself in playing the game. If self-repugnance is a fitting emotional response to playing a videogame, then this is prima facie grounds for thinking it is wrong to play the videogame. Our approach to the gamer’s dilemma is to distinguish the fittingness conditions of self-repugnance from the fittingness conditions of other moral emotions as they pertain to playing videogames. We argue that because of the virtual character of the actions performed in video games, self-repugnance is a fitting response to particular kinds of offensive gameplay. On the other hand, in-game murder is not invariably a fitting ground for self-repugnance. We argue that this difference is grounded in imaginative responses to the harm of death and the harms of profound suffering. Our task is to explain and justify this difference in fittingness conditions and use this to resolve the gamer’s dilemma.
Digital Transformation Stands Alongside Inclusive Education: Lessons Learned from a Project Called “Waking Up in the Morning”
Authors: Kaimara Polyxeni 
Published: July 2023

AbstractThe right of people with special educational needs and disabilities to be educated alongside their typically developing peers is a fundamental human right protected by national laws and international conventions. However, education systems around the world still face the challenge of providing effective education for all children and young people. Nowadays, academic research on the implementation of inclusive education has shifted from “where” students should be educated to “what” and “how” they should be taught. Although teachers express willingness to implement inclusive education pedagogy, they nevertheless state that they lack educational materials and even encounter difficulties in creating their educational resources due to a lack of expertise. In this context and under the current research imperatives in inclusive education regarding the benefits of digital transformation, an inclusive transmedia application based on gamification techniques, called “Waking Up In the Morning” (WUIM), was designed and developed to supply an integrated educational method that can be applied in inclusive learning environments. The purpose of WUIM providing content for teaching Activities of Daily Living is to emphasize the participatory design for developing inclusive learning materials, while also using formative assessment elements that actively engage end-user. The conclusions of the formative assessment were drawn from the data collected to answer the main research question: “Can educational applications, based on transmedia learning principles, cutting-edge technology and game elements support inclusive education?“. Since for every educational innovation, it is necessary to identify teachers’ opinions about it, two parallel surveys were conducted on teachers’ attitudes towards inclusive education and digital games for learning and teaching. Based on the results, it can be concluded that teachers were hesitant in both cases, a reluctance that was not solely driven by ideological barriers but also by a lack of training in educational practices. This work highlights the lessons learned about teachers’ attitudes regarding inclusive education and digital educational games, the pedagogical foundations of game design, the power of transdisciplinary teamwork, and the affordances of virtual reality, augmented reality and digital games to support education and treatment of individuals with special educational needs and/or disabilities in inclusive settings.
LGBT+ Self-Identification Among Youth in Ireland Aged 17-18 Years: A Research Brief
Authors: Ceatha Nerilee , Gates Gary J. , Crowley Des 
Published: July 2023

AbstractIn 2016, for the first time, a nationally representative survey of 6216 respondents, Growing Up in Ireland (GUI), included measurement of sexual orientation and gender identity (SOGI) among young people. Irish LGBTI+ youth and inclusion strategies identified collection of SOGI data as a policy objective, prioritizing analyses of GUI. In line with policy objectives, this research brief reports previously unpublished LGBT+ self-identification for youth in Ireland from Cohort ’98 born five years after decriminalization of homosexuality, with their coming-of-age coinciding with the marriage equality referendum, and legislation providing for greater gender recognition (2015). Ten percent of youth in Ireland, at 17-18 years, identify as lesbian, gay, bisexual, transgender, questioning, asexual or describe their gender as other. Female youth are significantly more likely to identify as a sexual minority, and to be bisexual than their male peers. A quarter of LGBT+ youth are questioning their sexual orientation. This finding supports the inclusion of a ‘questioning’ response in surveys collecting SOGI data, and also suggests sexual orientation self-identification is a dynamic process. A small percentage identify as asexual (0.2%). Just over 1% of young people identify as transgender or describe their gender as other. As the first generation in Ireland to grow up in an environment with increased LGBT+ visibility and social acceptance, these findings of a relatively high proportion of sexual and gender minorities among young people likely reflect improved social and legal climates. The importance of publication of SOGI estimates is underscored. GUI are committed to ensuring visibility of LGBT+ youth populations in data collection. Suggestions for improved SOGI placement and phrasing will be considered in the questionnaire with Cohort ’08 at age 17, currently being drafted. The findings from these analyses will inform future policy and research. GUI offers rich possibilities for future comparative cross-cohort analyses.