bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ustekinumab in pediatric patients with Crohn’s disease: safety, and efficacy results from a multicenter retrospective study in China
Authors: Li Ping , Wang Lin , Tang Zifei , Wang Yuhuan , Liu Zhanju , Ge Wensong , Huang Ying 
Published: April 2024

BackgroundUstekinumab (UST) is approved as an effective therapy for Crohn's disease (CD) in adults. Off-label use is increasing in the pediatric population, more data on safety and efficacy in pediatric patients with CD is urgently needed.AimsThis study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease.MethodsThis multicenter retrospective study carried out at three tertiary care centers, and identified children who received their first dose of UST at 18 years old or younger and followed up for a minimum of 24 weeks. Data on demographics, disease behavior, location and activity, treatment history were collected. The primary outcomes were clinical remission at weeks 24–32 and weeks 48–56 of UST therapy. Secondary outcomes were clinical response at the same time points, endoscopic remission, changes in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin and fecal calprotectin, improvement in growth parameters, and rate of adverse events.ResultsSixteen patients were included, and 11/13 (84.6%) continued to receive UST after 1 year. Our data demonstrate that the clinical remission rates were 41.7% at weeks 24∼32 with the Weighted pediatric CD activity index (wPCDAI) was lower than baseline (43.8, IQR: 31.3–51.9 vs.15, IQR: 5.6–25, p &lt; 0.001) and 75% at weeks 48–56 with wPCDAI was lower than baseline (42.5, IQR: 23.8–50 vs. 7.5, IQR: 0–13.8, p = 0.004). Five of eleven children achieved endoscopic remission. No serious adverse events were recorded during the study period.ConclusionsUST is efficacious and safe in pediatric patients with CD. Pediatric patients could benefit from UST as either a primary or secondary biologic therapy for the induction, or maintenance of remission of CD.
In vitro pharmacokinetics/pharmacodynamics of FL058 (a novel beta-lactamase inhibitor) combined with meropenem against carbapenemase-producing Enterobacterales
Authors: Huang Zhiwei , Bian Xingchen , Li Yi , Hu Jiali , Guo Beining , Yang Xinyi , Jin Yi , Zheng Shansong , Wang Xinmei , Gao Cong , Zhang Jing , Wu Xiaojie 
Published: April 2024

Objective: FL058 is a novel beta-lactamase inhibitor with a broad spectrum of activity and a favorable safety profile. The objective of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) relationships for the combination of FL058 and meropenem in an in vitro infection model.Methods: By simulating human concentration-time profiles in the in vitro model, meropenem combined with FL058 when administered 1 g/0.5 g, 1 g/1 g, 2 g/1 g, and 2 g/2 g q8h by 3-h infusion achieved approximately 2- and 4-log10 kill to KPC/OXA-producing Klebsiella pneumoniae and Escherichia coli; the combination therapy could not inhibit NDM-producing K. pneumoniae but could maintain NDM-producing E. coli around a baseline.Results: The PK/PD indexes that best described the bacterial killing from baseline in log10 CFU/mL at 24 h were the percent time of free drug above the minimal inhibitory concentration (MIC) (%fT &gt; MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT &gt; 1 mg/L) for FL058. The targets for achieving a static effect and the 1- and 2-log10 kill were 74, 83, and 99 for %fT &gt; MIC of meropenem and 40, 48, and 64 for %fT &gt; 1 mg/L of FL058, respectively. The PK/PD index of %fT &gt; 1 mg/L can provide a basis for evaluating clinical dosing regimens for FL058 combined with meropenem.Conclusion: FL058 combined with meropenem might be a potential treatment for KPC- and/or OXA-48-producing Enterobacterales infection.
Unveiling the magic of mega-city block environments: investigating the intriguing mechanisms shaping children’s spontaneous play preferences
Authors: Wang Yin , Sun Yinan , Sun Yihao , He Ting 
Published: April 2024

IntroductionThis study delves into the spatial preferences of children for play spaces within high-density urban block environments, specifically targeting the area of Baihua Second Road in Shenzhen, China.MethodsRecognizing the critical role of play in children’s development, and the unique challenges posed by dense urban settings, this research employs multiclass logistic regression models and negative binomial regression models to construct a detailed mathematical analysis of neighborhood spatial elements and children’s play space preferences. Data was meticulously gathered through both objective observations of 14 different types of spaces within the block, and subjective assessments via children’s responses to a series of environment photos, capturing the essence of over 3,000 child participants’ interactions and choices.ResultsKey findings reveal a pronounced preference among children for soft facility features and visually appealing spatial experiences, suggesting a nuanced understanding of play space needs beyond traditional playground designs. Notably, the study identifies that while cartoon-style designs in play facilities might increase moderate attractiveness, ordinary designs hold broader appeal, indicating a preference for diversity in play space aesthetics. These insights offer profound implications for urban planners and designers, advocating for a child-centered approach in the creation of urban play environments that prioritize aesthetic diversity, and the integration of natural elements.ConclusionMoreover, the study situates Baihua Second Road as a paradigmatic case, illustrating the methodology and analytical framework applied in addressing the complex interplay between children’s play preferences and urban spatial configurations. By incorporating a comprehensive data-driven analysis, this research contributes significantly to the discourse on child-friendly urban design, offering valuable strategies for cultivating inclusive and engaging urban play spaces for children amidst the constraints of high-density city living.
Exploring Spanish writing abilities of children with developmental language disorder in expository texts
Authors: Balboa-Castells Raquel , Ahufinger Nadia , Sanz-Torrent Mònica , Andreu Llorenç 
Published: April 2024

IntroductionNumerous studies have shown that children with developmental language disorder (DLD), in addition to oral language difficulties, exhibit impaired writing abilities. Their texts contain problems in grammar, organization, cohesion, and length of written output. However, most of these studies have been conducted with English speakers. English is characterized by complex phonological structure, opaque orthography, poor morphology and strict word order. The aim of this research is to observe the writing abilities of children with DLD in a language with simple phonological structure, transparent orthography, rich morphology and flexible word order like Spanish in the production of expository texts.MethodsTwenty-six children with DLD (mean age in months = 128.85) and 26 age-and sex-matched typically developing (TD) children (mean age in months = 124.61) wrote an expository text about their favorite animal.ResultsIn order to analyze how the two groups plan and encode written texts, we looked at word frequency and sentence structure, grammatical complexity and lexical density, and omissions and errors. Compared to the TD group, the children with DLD omitted more content words; made more errors with functional words, verb conjugation and inflectional morphemes, and made a large number of spelling errors. Moreover, they wrote fewer words, fewer sentences, and less structurally and lexically complex texts.DiscussionThese results show that children with DLD who speak a transparent orthography language such as Spanish also have difficulties in most language areas when producing written texts. Our findings should be considered when planning and designing interventions.
Compensatory brain activity pattern is not present in older adults during the n-back task performance—Findings based on EEG frequency analysis
Authors: Zając-Lamparska Ludmiła , Zabielska-Mendyk Emilia , Zapała Dariusz , Augustynowicz Paweł 
Published: April 2024

IntroductionCognitive ability is one of the most important enablers for successful aging. At the same time, cognitive decline is a well-documented phenomenon accompanying the aging process. Nevertheless, it is acknowledged that aging can also be related to positive processes that allow one to compensate for the decline. These processes include the compensatory brain activity of older adults primarily investigated using fMRI and PET. To strengthen the cognitive interpretation of compensatory brain activity in older adults, we searched for its indicators in brain activity measured by EEG.MethodsThe study sample comprised 110 volunteers, including 50 older adults (60–75 years old) and 60 young adults (20–35 years old) who performed 1-back, 2-back, and 3-back tasks while recording the EEG signal. The study analyzed (1) the level of cognitive performance, including sensitivity index, the percentage of correct answers to the target, and the percentage of false alarm errors; (2) theta and alpha power for electrodes located in the frontal-midline (Fz, AF3, AF4, F3, F4, FC1, and FC2) and the centro-parietal (CP1, CP2, P3, P4, and Pz) areas.ResultsCognitive performance was worse in older adults than in young adults, which manifested in a significantly lower sensitivity index and a significantly higher false alarm error rate at all levels of the n-back task difficulty. Simultaneously, performance worsened with increasing task difficulty regardless of age. Significantly lower theta power in the older participants was observed at all difficulty levels, even at the lowest one, where compensatory activity was expected. At the same time, at this difficulty level, cognitive performance was worse in older adults than in young adults, which could reduce the chances of observing compensatory brain activity. The significant decrease in theta power observed in both age groups with rising task difficulty can reflect a declining capacity for efficient cognitive functioning under increasing demands rather than adapting to this increase. Moreover, in young adults, alpha power decreased to some extent with increasing cognitive demand, reflecting adaptation to them, while in older adults, no analogous pattern was observed.DiscussionIn conclusion, based on the results of the current study, the presence of compensatory activity in older adults cannot be inferred.
Traumatic stress symptoms, mental splitting and burnout in health care professionals: a cross-sectional study
Authors: Riethof Norbert , Bob Petr 
Published: April 2024

BackgroundBurnout syndrome usually begins with feelings of enthusiasm and idealized visualizations, and it is in contrast with subsequent disillusionment, disappointment, and symptoms which are related to chronic stress experienced later. This tendency to idealization is a parallel to the concept of “mental splitting” described by Kernberg with a pronounced “black and white” perceptual dichotomy between the early idealization and later disillusionment. This study intends examination of relationships between burnout syndrome, traumatic stress and Kernberg’s concept of splitting.Methods and participantsIn this study we have assessed 90 health care professionals (50 women and 40 men) working with a population of diabetic patients utilizing Burnout Measure (BM), Splitting index (SI) and Traumatic Stress Checklist – 40 (TSC-40).ResultsStudy results indicate significant Spearman correlations between burnout syndrome (BM) and traumatic stress (TSC-40) in population of men (R=0.75, p&lt;0.01) and of women (R=0.61, p&lt;0.01), as well as between burnout syndrome (BM) and splitting (SI) for both genders: men (R=0.40, p&lt;0.01), women (R=0.51, p&lt;0.01). These findings may have implications for prevention and treatment of burnout syndrome.ConclusionThe current study findings provide implications that the defensive mechanisms of splitting and traumatic stress may allow for the prediction of burnout symptoms. This relation may potentially be of use in both the potential detection and prevention of burnout syndrome.
Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis
Authors: Lorenzo Erica C. , Figueroa Jovany E. , Demirci Derya A. , El-Tayyeb Ferris , Huggins Billy J. , Illindala Medha , Bartley Jenna M. , Haynes Laura , Diniz Breno S. 
Published: April 2024

Background: Little is known about the prevalence of cellular senescence among immune cells (i.e., immune cells expressing senescence markers, iSCs) nor is there a gold-standard to efficiently measure iSCs. Major depressive disorder (MDD) in older adults has been associated with many hallmarks of senescence in whole blood, leukocytes, and plasma, supporting a strong connection between iSCs and MDD. Here, we investigated the prevalence and phenotype of iSCs in older adults with MDD. Using a single-cell phenotypic approach, circulating immune cells were examined for iSC biomarkers and their relationship to depression and inflammation.Results: PBMCs from older adults with MDD (aged 69.75 ± 5.23 years) and healthy controls (aged 71.25 ± 8.8 years) were examined for immune subset distribution and senescence biomarkers (i.e., lack of proliferation, senescence-associated heterochromatin foci (SAHF), and DNA damage). Dual-expression of SAHF and DNA damage was categorized by low, intermediate, and high expression. A significant increase in the number of high expressing total PBMCs (p = 0.01), monocytes (p = 0.008), a trending increase in the number of high expressing CD4 T cells (p = 0.06) was observed overall in those with MDD. There was also a significantly lower proportion of intermediate expressing cells in monocytes and CD4 T cells in MDD (p = 0.01 and p = 0.05, respectively). Correlation analysis revealed associations between iSCs and mRNA expression of factors related to SASP and immune cell function.Conclusion: MDD is associated with increased senescent cell biomarkers in immune cell populations delineated by distinct levels of SAHF and DNA damage. Inflammatory markers might serve as potent indicators of iSC burden in MDD.
Sustainable integration of digitalisation in nursing education—an international scoping review
Authors: Tischendorf Tim , Heitmann-Möller André , Ruppert Sven-Nelson , Marchwacka Maria , Schaffrin Sandra , Schaal Tom , Hasseler Martina 
Published: April 2024

IntroductionTrainees and teachers at nursing schools as well as nursing professionals are increasingly facing new challenges as a result of the digital transformation. Opportunities for the entire care system exist in the improvement of care quality and communication between those involved. However, this change also harbours risks, such as the use of immature digital applications in the care sector, data theft and industrial espionage. In order to be able to exploit the potential of digitalisation despite these risks, it is necessary to integrate relevant aspects such as digital skills into nursing training. The aim of this study is to investigate the extent to which the sustainable integration of digitalisation in nursing education is discussed.MethodsThe methods of the systematic literature and database search were carried out in the form of a scoping review according to the PRISMA scheme. The PubMed and CINAHL databases were used for this purpose. The search period covered the years 2017–2023.FindingsAfter screening the titles and abstracts using inclusion and exclusion criteria, 13 studies were included in the synthesis of findings. The international literature focuses on content areas that highlight trends in digitalisation-related training in nursing. These focal points include concept development, considering the heterogeneity of demand constellations, as well as the reflexive reorientation of existing competences, whereby the technological competence of teachers is not disregarded. Other focal points relate to the initiation of digital skills in training and maintaining the employability of older nursing staff through professional development.DiscussionThe literature research shows that there is a rudimentary discussion about digitalisation and curricular developments in nursing training in an international context, while the discourse in the German-language literature is less advanced. Among the sustainability desiderata derived from the literature is the involvement of nursing professionals in the development, testing and implementation of digital technologies. Only through active cooperation between nursing professionals and nursing sciences can the topic of digitalisation be integrated into the education and training of professional nursing in a targeted and future-oriented manner, whereby the focus should always be on the ability to deal with digital technologies and the associated change.
Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols
Authors: Moreau Marjory , Simms Liam , Andersen Melvin E. , Trelles Sticken Edgar , Wieczorek Roman , Pour Sarah Jean , Chapman Fiona , Roewer Karin , Otte Sandra , Fisher Jeffrey , Stevenson Matthew 
Published: April 2024

With the use of in vitro new approach methodologies (NAMs) for the assessment of non-combustible next-generation nicotine delivery products, new extrapolation methods will also be required to interpret and contextualize the physiological relevance of these results. Quantitative in vitro to in vivo extrapolation (QIVIVE) can translate in vitro concentrations into in-life exposures with physiologically-based pharmacokinetic (PBPK) modelling and provide estimates of the likelihood of harmful effects from expected exposures. A major challenge for evaluating inhalation toxicology is an accurate assessment of the delivered dose to the surface of the cells and the internalized dose. To estimate this, we ran the multiple-path particle dosimetry (MPPD) model to characterize particle deposition in the respiratory tract and developed a PBPK model for nicotine that was validated with human clinical trial data for cigarettes. Finally, we estimated a Human Equivalent Concentration (HEC) and predicted plasma concentrations based on the minimum effective concentration (MEC) derived after acute exposure of BEAS-2B cells to cigarette smoke (1R6F), or heated tobacco product (HTP) aerosol at the air liquid interface (ALI). The MPPD-PBPK model predicted the in vivo data from clinical studies within a factor of two, indicating good agreement as noted by WHO International Programme on Chemical Safety (2010) guidance. We then used QIVIVE to derive the exposure concentration (HEC) that matched the estimated in vitro deposition point of departure (POD) (MEC cigarette = 0.38 puffs or 11.6 µg nicotine, HTP = 22.9 puffs or 125.6 µg nicotine) and subsequently derived the equivalent human plasma concentrations. Results indicate that for the 1R6F cigarette, inhaling 1/6th of a stick would be required to induce the same effects observed in vitro, in vivo. Whereas, for HTP it would be necessary to consume 3 sticks simultaneously to induce in vivo the effects observed in vitro. This data further demonstrates the reduced physiological potency potential of HTP aerosol compared to cigarette smoke. The QIVIVE approach demonstrates great promise in assisting human health risk assessments, however, further optimization and standardization are required for the substantiation of a meaningful contribution to tobacco harm reduction by alternative nicotine delivery products.
Implications of High Sensitivity Troponin Levels After Lung Transplantation
Authors: Rodenas-Alesina Eduard , Luk Adriana , Gajasan John , Alhussaini Anhar , Martel Genevieve , Serrick Cyril , McRae Karen , Overgaard Chris , Cypel Marcelo , Singer Lianne , Tikkanen Jussi , Keshavjee Shaf , Del Sorbo Lorenzo 
Published: April 2024

Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included. Hs-cTnI levels were collected at 0–24 h, 24–48 h and 48–72 h after LT. The primary outcome was invasive mechanical ventilation (IMV) &gt;3 days. 206 patients received a LT (median age 58, 35.4% women; 79.6% double LT). All patients but one fulfilled the criteria for postoperative myocardial infarction (median peak hs-cTnI = 4,820 ng/mL). Peak hs-cTnI correlated with right ventricular dysfunction, &gt;1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV&gt;3 days occurred in 91 (44.2%) patients, and peak hs-cTnI was higher in these patients (3,823 vs. 6,429 ng/mL, p &lt; 0.001 after adjustment). Peak hs-cTnI was higher among patients with had atrial arrhythmias or died during admission. No patients underwent revascularization. In summary, peak hs-TnI is determined by recipient comorbidities and perioperative factors, and not by coronary artery disease. Hs-cTnI captures patients at higher risk for prolonged IMV, atrial arrhythmias and in-hospital death.
Vector-Valued Fuzzy Metric Spaces and Fixed Point Theorems
Authors: Shukla Satish , Dubey Nikita , Miñana Juan-José 
Published: April 2024

The purpose of this paper is to generalize the concept of classical fuzzy set to vector-valued fuzzy set which can attend values not only in the real interval [0, 1], but in an ordered interval of a Banach algebra as well. This notion allows us to introduce the concept of vector-valued fuzzy metric space which generalizes, extends and unifies the notion of classical fuzzy metric space and complex-valued fuzzy metric space and permits us to consider the fuzzy sets and metrics in a larger domain. Some topological properties of such spaces are discussed and some fixed point results in this new setting are proved. Multifarious examples are presented which clarify and justify our claims and results.
Boosting Second Harmonic Generation Efficiency and Nonlinear Susceptibility via Metasurfaces Featuring Split-Ring Resonators and Bowtie Nanoantennas
Authors: Chou Chau Yuan-Fong 
Published: April 2024

This work investigates a metasurface design to achieve remarkable second harmonic generation (SHG) conversion efficiency and enhance effective nonlinear susceptibility using the finite element method. The elements of the designed structure are composed of a rectangular split-ring resonator Ag film, a bowtie-shaped Ag nanoantenna, and a pair of Bi bars that induce nonlinear optical phenomena due to the nonuniform distribution of the electric and magnetic fields within the device surface. The simulation results agree perfectly with the theory and demonstrate outstanding achievements in terms of SHG conversion efficiency (η) and effective nonlinear susceptibility (χeff(2)). Specifically, the metasurface reaches a peak η value of 4.544×10−8 and an effective nonlinear susceptibility of 3.4×104 pm/V. This work presents a novel and versatile design to achieve high η and χeff(2) in an SHG metasurface.