bluuebunny/crossref_metadata_2025 huggingface dataset:
Tastant-receptor interactions: insights from the fruit fly
Authors: Arntsen Christian , Guillemin Jacqueline , Audette Kayla , Stanley Molly
Published: April 2024

Across species, taste provides important chemical information about potential food sources and the surrounding environment. As details about the chemicals and receptors responsible for gustation are discovered, a complex view of the taste system is emerging with significant contributions from research using the fruit fly, Drosophila melanogaster, as a model organism. In this brief review, we summarize recent advances in Drosophila gustation and their relevance to taste research more broadly. Our goal is to highlight the molecular mechanisms underlying the first step of gustatory circuits: ligand-receptor interactions in primary taste cells. After an introduction to the Drosophila taste system and how it encodes the canonical taste modalities sweet, bitter, and salty, we describe recent insights into the complex nature of carboxylic acid and amino acid detection in the context of sour and umami taste, respectively. Our analysis extends to non-canonical taste modalities including metals, fatty acids, and bacterial components, and highlights unexpected receptors and signaling pathways that have recently been identified in Drosophila taste cells. Comparing the intricate molecular and cellular underpinnings of how ligands are detected in vivo in fruit flies reveals both specific and promiscuous receptor selectivity for taste encoding. Throughout this review, we compare and contextualize these Drosophila findings with mammalian research to not only emphasize the conservation of these chemosensory systems, but to demonstrate the power of this model organism in elucidating the neurobiology of taste and feeding.
Evaluating the feasibility and acceptability of an adapted fencing intervention in breast cancer surgery post-operative care: the RIPOSTE pilot randomized trial
Authors: Hasnaoui Sabrine , Van Hoye Aurélie , Soudant Marc , Rotonda Christine , Carvalho de Freitas Andréia , Peiffert Didier , Delattre Cécile , Raft Julien , Temperelli Margaux , Allado Edem , Hily Oriane , Chenuel Bruno , Hornus-Dragne Dominique , Omorou Abdou Y. , Poussel Mathias
Published: April 2024

Background

Adapted physical activity programs have shown promising results in reducing the physical, social and psychological side effects associated with breast cancer, but the extent to which they can be effectively adopted, implemented and maintained is unclear. The aim of this study is to use the framework to guide the planning and evaluation of programs according to the 5 following keys: Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate a fencing program under the French acronym RIPOSTE (Reconstruction, Image de soi, Posture, Oncologie, Santé, Thérapie, Escrime) literally in English (Reconstruction, Self-Image, Posture, Oncology, Health, Therapy, Fencing). This program is an innovative intervention focused on improving the quality of life (QoL) of breast cancer surgery patients through fencing.

Methods

A convergent mixed methods pilot study was conducted to preliminary evaluate the different RE-AIM dimension of the pilot program. Twenty-four participants who have just undergone surgery for invasive breast cancer were randomly allocated in two groups: one group started immediately after their inclusion (Early RIPOSTE group) and the other started 3 months following their inclusion (Delayed RIPOSTE group). Participants answered a questionnaire at inclusion and at the end of the program on QoL, shoulder functional capacity, fatigue, anxiety-depression and physical activity.

Results

RIPOSTE program was able to reach mainly young and dynamic participants, attracted by the originality of fencing and keen to improve their physical condition. Regarding effectiveness, our results suggest a trend to the improvement of QoL, shoulder functional capacity, fatigue and anxiety-depression state, even without any significant differences between the Early RIPOSTE group and the Delayed RIPOSTE group.

Discussions

The cooperation, exchanges and cohesion within the group greatly facilitated the adoption of the program, whereas interruptions during school vacations were the main barriers. The intervention was moderately well implemented and adherence to the protocol was suitable.

Conclusion

RIPOSTE is an acceptable and effective program for involving breast cancer survivors in physical activity, that needs to be tested at a larger scale to investigate its effectiveness, but has the potential to be transferred and scaled up worldwide.
Relationship between METS-IR and thyroid cancer incidence in Korea: a nationwide population-based study
Authors: Kim Hye Ryeon , Son Minkook , Huh Seok Jae , Moon Sang Yi , Moon Hyeyeon , Kang Yeo Wool , Koh Myeongseok , Lee Jong Yoon
Published: April 2024

Background

Several previous studies found a positive relationship between metabolic syndrome (MetS) and thyroid cancer (TC) risk. However, there is no research that has studied the relationship between the metabolic score for insulin resistance (METS-IR), a novel surrogate marker for IR, and TC incidence. Thus, we designed this retrospective cohort study to evaluate the relationship between the incidence of TC and METS-IR.

Method

We analyzed a cohort of 314,321 Korean adults aged over 40 years who participated in the National Health Screening Program from 2009 to 2010. The individuals were divided into four groups based on METS-IR quartiles. Follow-up was until the diagnosis of TC or death, or until December 31, 2019, if neither. The relationship between METS-IR and TC incidence was analyzed using the Cox proportional-hazards model with multi-variable adjustments.

Results

A total of 4,137 participants (1.3%) were diagnosed with TC during a mean follow-up of 9.5 ± 1.5 years. The population with Q1 METS-IR scores showed higher disease-free probabilities than those with Q4 METS-IR scores (p <0.001). The hazard ratio (95% confidential interval) for TC incidence in Q2, Q3, and Q4 METS-IR value were 1.14 (1.05 to 1.25), 1.21 (1.11 to 1.33), and 1.30 (1.18 to 1.42) compared with Q1 of METS-IR, respectively. The incidence of TC tended to increase with increasing METS-IR values in the total population, especially the male population in the restricted cubic spline. In subgroup analysis, the TC risk was more pronounced in the subgroups under 65 and with a BMI < 25 kg/m2.

Conclusion

METS-IR was positively correlated with TC incidence in Korea.
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

Background

Ustekinumab (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.

Aims

This study aimed to evaluate the clinical efficacy and safety of UST in children and adolescents with Crohn's disease.

Methods

This 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.

Results

Sixteen 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 < 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.

Conclusions

UST 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 > MIC, MIC with FL058 at 4 mg/L) for meropenem and the percent time of free drug above 1 mg/L (%fT > 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 > MIC of meropenem and 40, 48, and 64 for %fT > 1 mg/L of FL058, respectively. The PK/PD index of %fT > 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.
Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications
Authors: Zhang Senbing , Pu Yanzhu , Liu Jianning , Li Lewen , An Chibing , Wu Yumin , Zhang Wenjie , Zhang Wenxia , Qu Song , Yan Wenjun
Published: April 2024

(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson’s disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.
Ligand-based virtual-screening identified a novel CFTR ligand which improves the defective cell surface expression of misfolded ABC transporters
Authors: Taniguchi Shogo , Berenger Francois , Doi Yukako , Mimura Ayana , Yamanishi Yoshihiro , Okiyoneda Tsukasa
Published: April 2024

Cystic fibrosis (CF) is a monogenetic disease caused by the mutation of CFTR, a cAMP-regulated Cl− channel expressing at the apical plasma membrane (PM) of epithelia. ∆F508-CFTR, the most common mutant in CF, fails to reach the PM due to its misfolding and premature degradation at the endoplasmic reticulum (ER). Recently, CFTR modulators have been developed to correct CFTR abnormalities, with some being used as therapeutic agents for CF treatment. One notable example is Trikafta, a triple combination of CFTR modulators (TEZ/ELX/IVA), which significantly enhances the functionality of ΔF508-CFTR on the PM. However, there’s room for improvement in its therapeutic effectiveness since TEZ/ELX/IVA doesn't fully stabilize ΔF508-CFTR on the PM. To discover new CFTR modulators, we conducted a virtual screening of approximately 4.3 million compounds based on the chemical structures of existing CFTR modulators. This effort led us to identify a novel CFTR ligand named FR3. Unlike clinically available CFTR modulators, FR3 appears to operate through a distinct mechanism of action. FR3 enhances the functional expression of ΔF508-CFTR on the apical PM in airway epithelial cell lines by stabilizing NBD1. Notably, FR3 counteracted the degradation of mature ΔF508-CFTR, which still occurs despite the presence of TEZ/ELX/IVA. Furthermore, FR3 corrected the defective PM expression of a misfolded ABCB1 mutant. Therefore, FR3 may be a potential lead compound for addressing diseases resulting from the misfolding of ABC transporters.
ecGBMsub: an integrative stacking ensemble model framework based on eccDNA molecular profiling for improving IDH wild-type glioblastoma molecular subtype classification
Authors: Li Zesheng , Wei Cheng , Zhang Zhenyu , Han Lei
Published: April 2024

IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named “XGBoost.Enet-stacking-Enet” was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).
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

Introduction

This 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.

Methods

Recognizing 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.

Results

Key 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.

Conclusion

Moreover, 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

Introduction

Numerous 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.

Methods

Twenty-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.

Results

In 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.

Discussion

These 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

Introduction

Cognitive 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.

Methods

The 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.

Results

Cognitive 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.

Discussion

In 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

Background

Burnout 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 participants

In 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).

Results

Study results indicate significant Spearman correlations between burnout syndrome (BM) and traumatic stress (TSC-40) in population of men (R=0.75, p<0.01) and of women (R=0.61, p<0.01), as well as between burnout syndrome (BM) and splitting (SI) for both genders: men (R=0.40, p<0.01), women (R=0.51, p<0.01). These findings may have implications for prevention and treatment of burnout syndrome.

Conclusion

The 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

Introduction

Trainees 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.

Methods

The 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.

Findings

After 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.

Discussion

The 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) >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, >1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV>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 < 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.
A Mesh-Based Approach for Computational Fluid Dynamics-Free Aerodynamic Optimisation of Complex Geometries Using Area Ruling
Authors: Evans Ben James , Smith Ben , Walton Sean Peter , Taylor Neil , Dodds Martin , Zmijanovic Vladeta
Published: April 2024

In this paper, an optimisation procedure is introduced that uses a significantly cheaper, and CFD-free, objective function for aerodynamic optimisation than conventional CFD-driven approaches. Despite the reduced computational cost, we show that this approach can still drive the optimisation scheme towards a design with a similar reduction in drag coefficient for wave drag-dominated problems. The approach used is ‘CFD-free’, i.e., it does not require any computational aerodynamic analysis. It can be applied to geometries discretised using meshes more conventionally used for ‘standard’ CFD-based optimisation approaches. The approach outlined in this paper makes use of the transonic area rule and its supersonic extension, exploiting a mesh-based parameterisation and mesh morphing methodology. The paper addresses the following question: ‘To what extent can an optimiser perform (wave) drag minimisation if using ‘area ruling’ alone as the objective (fitness) function measurement?’. A summary of the wave drag approximation in transonic and supersonic regimes is outlined along with the methodology for exploiting this theory on a typical CFD surface mesh to construct an objective function evaluation for a given geometry. The implementation is presented including notes on the considerations required to ensure stability, and error minimisation, of the numerical scheme. The paper concludes with the results from a number of (simple and complex geometry) examples of a drag-minimisation optimisation study and the results are compared with an approach using full-fidelity CFD simulation. The overall conclusions from this study suggest that the approach presented is capable of driving a geometry towards a similar shape to when using full-fidelity CFD at a significantly lower computational cost. However, it cannot account for any constraints, driven by other aerodynamic factors, that might be present within the problem.
Dynamic Event-Triggered Prescribed Performance Robust Control for Aggressive Quadrotor Flight
Authors: Wu Zeliang , Ye Jianchuan , Song Tao
Published: April 2024

Aggressive flight has become increasingly important for expanding the applications of quadrotors. The typical characteristic of large and rapid changes in commands poses stringent demands on the maneuverability of quadrotors. Ensuring flight stability alone is not enough; dynamic responses must also be selectively constrained, presenting quadcopter flight control with daunting challenges. The prescribed performance control (PPC) method is seen as having the potential to solve this problem by allowing for the constrained control of specified performance, leading to extensive research. However, its practical application still faces challenges, such as the system divergence caused by errors exceeding boundaries due to sudden command mutations. This paper presents a robust dynamic event-triggered PPC (DETPPC) method for an aggressive quadrotor flight. By assessing the direction and proximity of tracking errors approaching constraint boundaries, a dynamic event-triggered compensation mechanism for performance function boundaries is established to mitigate the divergence caused by error surpassing and to preserve preset control over the targeted metrics. Controllers were designed for both the translational and rotational subsystems of the quadrotor, and stability analysis was conducted based on Lyapunov functions. Simulation tests on agile trajectory tracking and abrupt attitude control were carried out, demonstrating the effectiveness of the proposed method.
Efficacy of Intravaginal Lactic Acid Bacteria, Cell-Free Supernatant, or Enrofloxacin on Vaginitis and Fertility in Ewes Synchronized with Progesterone-Based Protocol
Authors: Guner Baris , Ayalp Erkan Aslihan , Ozturk Buse , Guner Tevhide Elif , Kisadere Ihsan , Demirbilek Serpil Kahya , Keskin Abdulkadir , František Zigo
Published: April 2024

An intravaginal sponge impregnated with progesterone is commonly used for estrus induction and synchronization in ewes. Although using an intravaginal sponge containing progesterone positively affects the synchronization rate, varying degrees of vaginitis occur during its application. This study aimed to investigate the impacts of various intravaginal treatment options on the vaginitis severity and pregnancy rate in Merino ewes synchronized with intravaginal sponges impregnated with progesterone. During the breeding period, 589 ewes, aged 2–6, received intravaginal sponges for 14 days. The control group (CON) received no treatment, whereas vaginal sponges absorbed with enrofloxacin (ENR), Lactobacillus plantarum (LAC), or Lactobacillus plantarum supernatant (CFS) were applied in the treatment groups. All groups received 500 IU of equine chorionic gonadotropin intramuscularly. The ENR group showed lower scores in vaginal discharge and sponge odor compared with the CON, LAC, and CFS groups. Although estrus responses did not differ between groups, the pregnancy rate tended to be higher in the ENR group. In conclusion, intravaginal ENR application, but not LAC or CFS, reduced vaginitis severity and tended to increase pregnancy rates in ewes synchronized with intravaginal sponges impregnated with progesterone.
Synergistic Effects of Chemical Fungicides with Crude Extracts from Bacillus amyloliquefaciens to Control Northern Corn Leaf Blight
Authors: Wang Meng , Duan Haiming , Zhou Cheng , Yu Li , Meng Xiangtao , Lu Wenjie , Yu Haibing
Published: April 2024

In this research, our objective was to investigate the combined impact of microbial extracts and chemical fungicides on Northern corn leaf blight (NCLB), which is induced by Exserohilum turcicum, and the growth-promoting effect of the crude extracts was also determined. NCLB poses a serious threat to global maize production, necessitating sustainable and environmentally friendly solutions. Mycelial growth rate assays were used to assess the single or synergistic effects of microbial crude extracts and chemical fungicides, and the seed-soaking and root irrigation method was used to detect the growth-promoting effect of the crude extracts on maize seedlings. The results revealed an 84.60% inhibition rate of B. amyloliquefaciens gfj-4 against E. turcicum, and with an EC50 of 49.01 mg·L−1 for the crude extracts. Chemical fungicides demonstrated varying toxicity levels, with fludioxonil exhibiting the highest potency. The mixture of the crude extracts and pyraclostrobin at an 8:2 volume ratio displayed the highest toxicity ratio of 1.24, indicating a synergistic effect. The selected combinations exhibited strong synergistic effects. Soaking maize seeds with 80 mg·L−1 of the crude extracts followed by root irrigation with 40 mg·L−1 produced the most significant growth-promoting effect on maize seedlings. This study highlights the potential of microbial crude extracts to enhance the control of NCLB when combined with pyraclostrobin, along with its growth-promoting effects on maize seedlings.
Combination Effects of Sulfur Fertilizer and Rhizobium Inoculant on Photosynthesis Dynamics and Yield Components of Soybean
Authors: Bi Yingdong , Fan Chao , Liang Wenwei , Liao Yi , Han Dezhi , Li Wei , Chen Xiangjin , Liu Miao , Liu Jianxin , Di Shufeng , Yang Guang , Wang Yufeng , Liu Yuehui , Lai Yongcai , Lu Wencheng , Li Guotai
Published: April 2024

Sulfur (S) fertilization and rhizobium inoculation are important agronomic practices for improving soybean growth and yield. However, their combined effects on yield components and the resultant impacts on yield need further investigation. Our study aimed to verify the combined effects of S fertilizer and rhizobium inoculant on the yield components and seed yield of soybeans, as well as photosynthesis dynamics during the V5–R6 growth stages. A randomized block design incorporating two factors was employed for field experiments on soybean, involving the application of five rates of sulfur (0, 5.0, 9.8, 14.8, and 19.6 kg S ha−1) with rhizobium inoculation or without. A reduction of 50% in mineral fertilizer according to farmer practice (FP) was applied alongside different rates of sulfur for field experiments on soybeans. The findings indicated that the application of sulfur fertilization significantly enhanced soybean yield by increasing the number of grains per plant (NG) and the number of pods per plant (NP). Maximum grain yield was reached under treatment with an S rate of 19.6 kg S ha−1, which increased NG by 39% more than an S rate of 0 kg S ha−1. Correlation analysis indicated that higher photosynthesis was closely associated with increased yield components. This study demonstrated that applying S fertilizers could improve soybean production by combining the appropriate sulfur concentration and rhizobia inoculation.
Pre-Slaughter Stunning Methods Influence the Meat Quality of Arapaima gigas Fillets
Authors: Braitenbach Cavali Jucilene , Vargas Baldi Sheyla Cristina , Coutinho Marques Rocha Ana Sabrina , Eloy da Silva Erica , Taveira Nunes Carla , Soares Emerson Carlos , de Vargas Schons Sandro , Zanella Renato , Bianchini Pontuschka Rute , Vieira Dantas Filho Jerônimo
Published: April 2024

The aim of this study was to evaluate the influence of different stunning methods on the meat quality of Arapaima gigas fillets from fish farming. A total of 48 specimens of A. gigas in the weight class 11.1 to 14.0 kg were investigated; these fish were subjected to different stunning methods for slaughter: ice asphyxia (IA), air asphyxia (AA), electronarcosis (EE) and hypothermia followed by bleeding (HB). Then, data were obtained from the analysis of pH, rigor mortis index (RI), water activity (Aw), instrumental texture (compression strength, firmness and adhesiveness) and blood glucose and via instrumental colourimetry. During the study, for up to 15 days of refrigerated storage, the methods provided pH values below 6.0. A. gigas submitted to EE and HB remained longer in the pre-rigor status. In addition, they expressed lower percentages of Aw. The EE method resulted in better texture assignments in the fillets. The blood glucose values indicated that the fish subjected to EE were less stressed. Concerning instrumental colourimetry, the fillets submitted to EE and HB showed greater luminosity; the fillets subjected to AA showed greater red-green colour intensity, while the fillets subjected to EE showed greater yellow-blue colour intensity. Therefore, the fish did not suffer stress with electronarcosis, and the fillets showed better preservation, juiciness, and tenderness.
Dietary Artemisia arborescens Supplementation Effects on Growth, Oxidative Status, and Immunity of Gilthead Seabream (Sparus aurata L.)
Authors: Tzortzatos Odysseas-Panagiotis , Toubanaki Dimitra K. , Kolygas Markos N. , Kotzamanis Yannis , Roussos Efstratios , Bakopoulos Vasileios , Chatzopoulos Achilleas , Athanassopoulou Fotini , Karagouni Evdokia
Published: April 2024

Fish infectious diseases are one of the main constraints of the aquaculture sector. The use of medicinal plants provides a sustainable way of protection using safe, eco-friendly compounds in a more cost-effective way of treatment, compared to antibiotics. The aim of the present study is the assessment of Artemisia arborescens (AA) feed-supplementation effects on gilthead seabream (Sparus aurata). Fish with an average initial body weight of 109.43 ± 3.81 g, were divided into two groups based on AA feed composition (A25 and A50). Following two months of ad libitum feeding, the effect of diets on fish weight and length were measured. Fish serum and mucus were analyzed for non-specific immune parameters (nitric oxide, lysozyme, myeloperoxidase, protease-/anti-protease activity, and complement), antibody responses, oxidative stress (cytochrome P450 1A1, metallothionein), and metabolism markers (total protein, alkaline phosphatase, and glucose). Expression levels of antioxidants (sod1, gpx1), cytokines (il-1b, il-10, tfgb1, and tnfa), hepcidin, and heat shock protein grp75 genes were measured in spleen samples. A results analysis indicated that A. arborescens use as a feed supplement has a compromised positive effect on the growth performance, immune response, and blood parameters of gilthead seabream. Overall, the suitability of A. arborescens as an efficient food supplement for gilthead seabream health improvement was investigated, setting the basis for its application assessment in Mediterranean aquaculture.