bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of physical frailty on maximum phonation time in community‐dwelling older individuals who visited a neurology outpatient clinic
Authors: Umehara Ken , Yamamoto Akio , Kitagawa Takeo , Yoshimaru Kimiko , Ishikawa Akira
Published: April 2024

Background

Maximum phonation time (MPT) is used to assess speech and other oral rehabilitation‐related issues. Various factors contribute to MPT decline in older individuals. Although the impact of physical frailty on MPT has been suggested, this has not been conclusively determined.

Objective

To examine the relationship between MPT and physical frailty in community‐dwelling individuals aged ≥60 years who were independently mobile. MPT‐associated factors were investigated.

Methods

This cross‐sectional study analysed the clinical data of 122 patients (age [interquartile range]: 80.0 [74.0–83.0] years) without dementia who visited a neurology department between 1 February 2021 and 31 January 2023. Investigated factors included age, sex, weight, height, body mass index, smoking history, grip strength, functional independence measure, vital capacity, oral diadochokinesis, MPT and the Japanese Cardiovascular Health Study score. Physical frailty was assessed based on the total score from five items (weight loss, weakness, exhaustion, slowness and low physical activity). The relationship between MPT and physical frailty was examined using Spearman's rank correlation coefficient and hierarchical multiple regression analysis.

Results

The MPT was negatively correlated with age (r = −0.347, p < .01) and physical frailty (r = −0.681, p < .01) and positively correlated with vital capacity (r = 0.474, p < .01) and height (r = 0.248, p < .01). The hierarchical multiple regression analysis, conducted with MPT as the dependent variable, demonstrated that physical frailty (β = −.59, 95% confidence interval: −0.74 to 0.43, p < .001) had a strong influence on MPT.

Conclusion

In older individuals, MPT is associated with physical frailty. When assessing MPT in clinical settings, it is advisable to perform a concurrent assessment of physical frailty.
Efficacy of wireless sensors in assessing occlusal and bite forces: A systematic review
Authors: Ardila Carlos‐M. , Jiménez‐Arbeláez Gustavo A. , Vivares‐Builes Annie Marcela
Published: April 2024

Background

The noteworthy correlation between bite force and masticatory performance emphasizes its significance as a meaningful and objective method for assessing oral function. Furthermore, in the study of bruxism, the measurement of intraoral bite force assumes critical importance. Given the importance of assessing occlusal forces and bite force, this systematic review aims to assess the efficacy of wireless sensors in measuring these forces.

Methods

The search methodology employed in this systematic review adhered to the guidelines outlined by PRISMA. The strategy involved the exploration of various databases, including PubMed/MEDLINE, SCOPUS and SCIELO. An assessment tool was employed to evaluate the bias risk and study quality.

Results

This systematic review encompassed six prospective clinical studies involving a total of 89 participants. Wireless sensors for measuring occlusal forces and bite forces were predominantly employed in healthy adults or individuals with bruxism, along with children undergoing orthodontic treatment. All wireless sensors employed in the studies underwent validation and reproducibility assessments, affirming their reliability. The findings indicated that all wireless sensors exhibited efficacy in detecting occlusal forces and bite forces.

Conclusion

Wireless sensors offer real‐time monitoring of occlusal and bite forces, aiding in understanding force distribution and identifying bruxism patterns. Despite limited studies on their application, these sensors contribute to evolving insights. Integration into clinical practice requires careful consideration of factors like calibration and patient compliance. Ongoing research is crucial to address limitations and enhance the efficacy of wireless sensors in measuring occlusal and bite forces and managing bruxism.
A systematic review of the effectiveness of attentional bias modification to support weight management in individuals who are overweight or obese
Authors: Seage Catherine Heidi
Published: April 2024

Attentional bias modification (ABM) is a novel cognitive‐based treatment that may help individuals reduce overeating by decreasing food processing bias and food cravings. However, most empirical studies have evaluated the short‐term effects of ABM in populations that have body mass indexes that are within healthy ranges; therefore, the extent to which this training method can influence eating behavior in individuals who are overweight or obese remains unclear. This systematic review explored the efficacy of ABM as a tool to support weight management for individuals who are overweight or obese. Ten studies met the inclusion criteria for the review. The findings reveal that although training is effective at manipulating attentional bias to food cues, there is limited evidence that training significantly impacted appetite and eating behaviors or led to maintained weight loss.
Does the Sagittal Radiographic Morphology of Subtalar Joint Affect the Alignment of Foot?
Authors: Xu Yang , Zhu Yuan , Cao Yong‐xing , Chen Gang , Xu Xiang‐yang
Published: April 2024

Objectives

The etiology of flatfoot and cavus foot is multicausal and controversial. So far, no literature reports the relationship between the sagittal morphology of subtalar joint and the alignment of foot. The purpose of this study was to explore whether the subtalar alignment would influence the configuration of foot.

Methods

From January 2017 to January 2020, we included 109 feet in the flatfoot group, 95 feet in the cavus group, and 104 feet in the control group in this retrospective comparative study. The Gissane angle and calcaneal posterior articular surface inclination angle represented the sagittal morphology of the subtalar joint. Meary's angle, calcaneal pitch angle, and talar pitch angle reflected the alignment of foot. They were measured in the weightbearing foot X‐rays. The angles in different groups were compared via Mann–Whitney U test. We calculated the correlation between the sagittal alignment of subtalar joint and the alignment of foot using Spearman's correlation analysis. Interobserver and intraobserver reliability were calculated.

Results

The Gissane angle, calcaneal posterior articular surface inclination angle, Meary's angle, talar pitch angle, and calcaneal pitch angle were significantly different in the three groups. The Gissane angle had an excellent correlation with the Meary's angle (r = 0.850, p < 0.0001), and the talar pitch angle (r = −0.825, p < 0.0001), and a good correlation with the calcaneal pitch angle (r = 0.638, p < 0.0001). The calcaneal posterior articular surface inclination angle had an excellent correlation with the Meary's angle (r = −0.902, p < 0.001), and the talar pitch angle (r = 0.887, p < 0.0001), and a good correlation with the calcaneal pitch angle (r = −0.702, p < 0.0001). The interobserver and intraobserver reliability for all radiographic measurements was good to excellent.

Conclusion

A subtalar joint with a larger Gissane angle and a more horizontal calcaneal posterior articular surface angle tended to have a higher foot arch and vice versa. The inspiration from this study was that the deformities of flatfoot and cavus foot may relate to the subtalar deformity.
A novel approach to reducing hepatotoxicity related to fungal prophylaxis in pediatric lung transplant recipients
Authors: Patz‐Sobczak Caroline , Young Jennifer , Bunton Dawn , Kuklinski Cadence , Estabrook Michele
Published: April 2024

Background

Pediatric lung transplant patients are at risk for developing invasive fungal infections post‐transplant. No consensus exists on optimal antifungal regimens and voriconazole, a common first‐line agent, has been shown to cause hepatotoxicity. We describe a single‐center experience utilizing a novel antifungal regimen of intravenous micafungin and nebulized amphotericin B immediately post‐transplant with conversion to an azole at the time of hospital discharge and compare it to a historical cohort of patients who received voriconazole monotherapy throughout their immediate post‐operative course.

Methods

This is a retrospective review of patients in the age 0–18 who received a lung transplant from June 2016–May 2021. Data points collected included: demographic data, transplant date and discharge date, Aspergillus colonization, type of lung transplant, hospitalization and level of care information, induction and antifungal medication regimen; AST, ALT, GGT, bilirubin, and direct bilirubin at various timepoints; and respiratory and blood culture results. The two patient groups were compared by assessment of changes in LFTs and culture results.

Results

Forty‐two patients were included in the analysis, with 24 patients receiving micafungin and nebulized amphotericin and 18 patients receiving voriconazole. All patients in both groups experienced a post‐operative elevation in at least one transaminase or bilirubin. More patients in the micafungin/amphotericin group had resolution of all abnormal LFTs by 1 month post‐transplant (p = .036). Additionally, patients in the micafungin/amphotericin group experienced faster normalization of their LFTs compared with the voriconazole group (p < .001). Ten patients in the micafungin/amphotericin group and five patients in the voriconazole group were found to have fungal growth on culture post‐transplant, but this difference was not found to be statistically significant (p = .507).

Conclusions

An antifungal regimen of micafungin and nebulized amphotericin B liposomal may be useful at decreasing the duration of elevated liver enzymes in pediatric patients in the immediate post‐lung transplant period when compared with voriconazole monotherapy. Larger prospective studies looking at antifungal regimens in pediatric patients post‐lung transplant are warranted.
Assessing the drivers and capabilities for faster product launch: a scale for time‐to‐market reduction in start‐ups
Authors: Mota Renata de Oliveira , Godinho Filho Moacir , Ganga Gilberto Miller Devos , da Silva Jonhatan Magno Norte , Mendes Glauco Henrique de Sousa
Published: April 2024

The acceleration of new product development (NPD) and market introduction is essential for companies to maintain competitiveness, enhance customer base, and achieve financial success. While the existing literature addresses time‐to‐market (TTM) reduction factors in a scattered manner, focusing on aspects like supplier and customer involvement, leadership, and learning, there is a noticeable gap in construct development and measurement validation for TTM reduction, particularly in start‐up contexts. Addressing this gap, our research introduces and validates a comprehensive, hierarchical scale designed to measure both the drivers and capabilities associated with TTM reduction in start‐ups. This innovative scale broadens the scope of traditional constructs, incorporating emerging dimensions such as transformational leadership, experiential learning, agile methodologies, and dynamic marketing strategies. We used our dataset and structural equation modeling (SEM) to validate the proposed scale, comparing the effect of drivers and capabilities on TTM reduction and the role of companies' age on this relationship. This approach confirms the scale's reliability and highlights its versatility. This research holds significant implications for enhancing NPD endeavors in start‐up environments. Introducing a methodologically robust scale equips managers with a powerful tool for setting realistic goals, monitoring progress, and assessing capabilities and contextual factors to refine NPD processes. Furthermore, the scale serves as a benchmarking instrument for start‐ups, aiding them in attracting investments and achieving a competitive advantage. Our study, therefore, stands as an essential contribution to the strategic management of NPD in the dynamic and evolving landscape of start‐ups.
Electrical stimulation of the lower eyelid orbicularis oculi muscle improves periocular dark circles
Authors: Yasui Yukiko , Kato Hiroshi , Ogura Shuntaro , Kimura Masayo , Kato Aki , Hirano Yoshio , Morita Hiroshi , Yasukawa Tsutomu , Kurachi Ako , Takeda Soshi , Morita Akimichi
Published: April 2024

Background

We developed and tested the safety and efficacy of a cosmetic device to improve dark circles using electrical muscle stimulation of the orbicularis oculi muscle.

Methods

Overall, 18 participants (36 eyes) were studied. The following five items were evaluated before and after the intervention:(1) the Clinical Dark Circle Score using clinical findings and photographs, (2) transcutaneous oxygen partial pressure (TcPO2) on the lower eyelid, (3) thermography, (4) two‐dimensional laser blood flowmetry, and (5) spectrophotometry.

Results

The mean score at baseline was 2.0 ± 0.90 (mean ± standard deviation), and that at the end of the study was 1.2 ± 1.0 (Wilcoxon signed‐rank sum test, p < 0.0001), indicating a significant reduction. The spectrophotometer showed a significant decrease in a* and L* values before and after use (Wilcoxon signed‐rank sum test, p < 0.0001). There was also a weak negative correlation between the change in score and the change in blood flow and TcPO2 measured using a laser perfusion device (Spearman's rank correlation coefficient, r = –0.32 and –0.39, respectively). Stratified analysis of the baseline score showed a strong negative correlation between the change in score and the change in spectrophotometric a* in the subjects/group with mild periocular dark circles (Spearman's rank correlation coefficient, r = –0.46). Contrastingly, no correlation was observed for any of the measurements in the subjects/group with severe periocular dark circles. After 1 month, no device‐related ophthalmic adverse events were observed in any of the participants.

Conclusion

Electrical muscle stimulation could improve periocular dark circles, especially in the subjects/group with mild periocular dark circles, and was safe.
Effects on keratinocytes of the traditional combination of herb extract (Royal Oji Complex) implicated the improvement of young children's skin moisture and barrier
Authors: Trinh Thuy‐Tien Thi , Choi Jae Hee , Yang Jee‐Eun , Kim Woon Ha , Chien Pham Ngoc , Le Linh Thi Thuy , Ngan‐Giang Nguyen , Nga Pham Thi , Nam Sun‐Young , Heo Chan‐Yeong
Published: April 2024

Background

Natural products are often friendly and can be used on children's skin after systematic and careful research. Therefore, in this study, the Royal Oji Complex (ROC), a product with natural ingredients, was used to study their effectiveness on keratinocytes taken from the skin of children from 0 to 3 years old.

Method

Normal human epidermal keratinocytes and tissue‐isolated keratinocytes (TIKC) from young donors were treated with three different concentrations of ROC: 0.1, 1, and 10 ppm. The mRNA expression of the epidermal barrier's essential genes, such as hyaluronic acid synthase 3 (Has3), involucrin (IVL), loricrin (LOR), and claudin‐1 (CLD1) was investigated using qRT‐PCR. Ceramide content was measured by ELISA, with retinoic acid (R.A.) and amarogentin (AMA) serving as positive controls.

Results

ROC significantly elevated HAS3 gene expression in HEKn cells, especially at 10 ppm, indicating potential advantages for skin hydration in young infants. IVL increased at first but decreased as ROC concentrations increased. LOR was upregulated at lower ROC concentrations but reduced at higher doses. CLD1 gene expression increased considerably in HEKn but reduced with increasing ROC doses. Ceramide concentration increased somewhat but not significantly at 10 ppm.

Conclusion

ROC shows potential in altering keratinocyte gene expression, with unique responses in HEKn and TIKC from young donors. While changes in ceramide content were insignificant, these results help to comprehend ROC's multiple effects on young children's skin.
Monopole Floer homology and invariant theta characteristics
Authors: Lin Francesco
Published: April 2024

We describe a relationship between the monopole Floer homology of three‐manifolds and the geometry of Riemann surfaces. For an automorphism of a compact Riemann surface with quotient , there is a natural correspondence between theta characteristics on which are invariant under and self‐conjugate structures on the mapping torus of . We show that the monopole Floer homology groups of are explicitly determined by the eigenvalues of the (lift of the) action of on , the space of holomorphic sections of , and discuss several consequences of this description. Our result is based on a detailed analysis of the transversality properties of the Seiberg–Witten equations for suitable small perturbations.
Numerical Analysis of Soil Deformation in Earth Dams Using a Stiffness Variation Technique
Authors: Guerreiro Maia Romario Anderson , Da Silva Filho Francisco Chagas
Published: April 2024

Small earth dams have been used since ancient times and are often the main source of water in semi-arid regions. In this particular type of engineering work, soils saturated by water present changes in their mechanical properties (especially in the first filling), which usually cause a simultaneous loss of stiffness and shear strength. In this context, the software UNSTRUCT presents itself as a very useful tool, as it allows calculating the final state of stress x strain for a plane strain state, using the Finite Element Method, both for saturated and unsaturated embankments, considering an elastic model and the effect of suction (and its variation), through a stiffness variation technique. The present research used UNSTRUCT to assess the behavior of the embankment of a hypothetical earth dam, varying the features of its typical cross-section: homogeneity; internal drainage structures; geometry along a longitudinal profile; and the influence of the compaction level. The results showed that the soil responded better to strains for the scenario of better compaction along the dry branch of the compaction curve, as well as with the use of a vertical drainage element. It was also observed that the strains were higher when greater sections considered, which, in a real situation, would cause distortions along the longitudinal profile of the dam. The software UNSTRUCT proved to be efficient in obtaining and visualizing the modeling results, also making it possible to analyze the development of failure over time after the dam was filled. With UNSTRUCT, a more realistic analysis of the behavior of the hypothetical dam – considering factors that are specific to unsaturated soils – was possible. Worth mentioning also that the software allowed the appraisal of multiple changes in the dam’s geometry and parameters.
Aerodynamic Performance Evaluation of a Coaxial Octocopter Based on Taguchi Method
Authors: Geydirici Evren , Derman Kuzey C. , Cadirci Sertac
Published: April 2024

The design and optimization of propellers for unmanned aerial vehicles (UAVs) are essential for optimal performance and high efficiency. This study presents a numerical investigation of the aerodynamic performance of coaxial octocopters using openfoam as flow solver. While the aerodynamic performance is affected by many parameters, the current study focuses on four main parameters: the propeller type, the horizontal and vertical separation distances between the propellers, and the ratio between the rotational speeds of the upper propeller and the lower one. To find the minimum number of simulations to be performed within defined limits, and reduce the number of computational fluid dynamics (CFD) simulations that cause high computational cost, Taguchi method was employed. In this study, average thrusts were calculated for the preliminary design of the octocopter by examining an isolated single propeller and dual- and quad propellers taking their rotation directions into account. The Taguchi design matrix revealed that for all cases investigated, the propeller type is the most dominant design parameter followed by the velocity ratio of the upper propeller to the lower one (nU/nL) and vertical (z/D) and horizontal (ℓ/D) orientation of coaxial propellers. However, it was shown that ℓ/D and z/D may play a significant role in vortex formation and pressure fluctuations which should be considered as design criteria for coaxial octocopters associated with flow attributes. The results showed that the aerodynamic performance parameters are not dependent on all the selected parameters, and demonstrated that the selected propeller designs improved aerodynamic performance.
Capturing Local Temperature Evolution During Additive Manufacturing Through Fourier Neural Operators
Authors: Chen Jiangce , Xu Wenzhuo , Baldwin Martha , Nijhuis Björn , den Boogaard Ton van , Grande Gutiérrez Noelia , Prabha Narra Sneha , McComb Christopher
Published: April 2024

High-fidelity, data-driven models that can quickly simulate thermal behavior during additive manufacturing (AM) are crucial for improving the performance of AM technologies in multiple areas, such as part design, process planning, monitoring, and control. However, complexities of part geometries make it challenging for current models to maintain high accuracy across a wide range of geometries. In addition, many models report a low mean-square error (MSE) across the entire domain of a part. However, in each time-step, most areas of the domain do not experience significant changes in temperature, except for the regions near recent depositions. Therefore, the MSE-based fidelity measurement of the models may be overestimated. This article presents a data-driven model that uses the Fourier neural operator to capture the local temperature evolution during the AM process. Besides MSE, the model is also evaluated using the R2 metric, which places great weight on the regions where the temperature changes significantly than MSE. The model was trained and tested on numerical simulations based on the discontinuous Galerkin finite element method for the direct energy deposition AM process. The results shows that the model maintains 0.983−0.999 R2 over geometries not included in the training data, which is higher than convolutional neural networks and graph convolutional neural networks we implemented, the two widely used architectures in data-driven predictive modeling.
Do Parental Beliefs and Support Predict the Motor Competence of Youth With Visual Impairments?
Authors: Stribing Alexandra , Gilbert Emily N. , Lieberman Lauren J. , Brian Ali
Published: April 2024

Parents tend to play a vital role in their child’s motor competence for youth with visual impairments. However, little research has explored parental mindsets and support (e.g., transportation) surrounding their child’s motor skills and how it may predict motor competence. The purpose of this study was to examine the extent to which parents’ mindset items along with parental support may predict their children’s actual motor competence. Parents of youth with visual impairments (N = 92; mothers = 69.5%, fathers = 18.1%; Mage = 42.91 years, SD = 8.08 years) completed the modified parents’ perception questionnaire. Youth with visual impairments ages 9–19 years (N = 95; Mage = 153.35 months, SD = 27.58 months, girls = 37.1%, boys = 53.3%, 9.6% missing) completed the Test of Gross Motor Development-third edition. Results from a backward linear regression convey parental beliefs (i.e., growth mindsets) and support variables (e.g., providing transportation) significantly predicted their child’s actual motor competence, F(6, 84) = 9.77, p < .001, adj. R2 = .37. Results could inform parents on their importance toward supporting and believing in developing their child’s motor competence.
Combination of ganciclovir and trifluridine prevents drug-resistance emergence in HSV-1
Authors: Schalkwijk Hanna Helena , Shewakramani Neesha Rajesh , Das Kalyan , Andrei Graciela , Snoeck Robert
Published: April 2024

Ocular herpes simplex virus 1 (HSV-1) infections can lead to visual impairment. Long-term acyclovir (ACV) prophylaxis reduces the frequency of recurrences but is associated with drug resistance. Novel therapies are needed to treat drug-resistant HSV-1 infections. Here, we describe the effects of trifluridine (TFT) in combination with ACV or ganciclovir (GCV) on HSV-1 replication and drug-resistance emergence. Wild-type HSV-1 was grown under increasing doses of one antiviral (ACV, GCV, or TFT) or combinations thereof (ACV + TFT or GCV + TFT). Virus cultures were analyzed by Sanger sequencing and deep sequencing of the
UL23
[thymidine kinase (TK)] and
UL30
[DNA polymerase (DP)] genes. The phenotypes of novel mutations were determined by cytopathic effect reduction assays. TFT showed overall additive anti-HSV-1 activity with ACV and GCV. Five passages under ACV, GCV, or TFT drug pressure gave rise to resistance mutations, primarily in the TK. ACV + TFT and GCV + TFT combinatory pressure induced mutations in the TK and DP. The DP mutations were mainly located in terminal regions, outside segments that typically carry resistance mutations. TK mutations (R163H, A167T, and M231I) conferring resistance to all three nucleoside analogs (ACV, TFT, and GCV) emerged under ACV, TFT, ACV + TFT pressure and under GCV + TFT pressure initiated from suboptimal drug concentrations. However, higher doses of GCV and TFT prevented drug resistance in the resistance selection experiments. In summary, we identified novel mutations conferring resistance to nucleoside analogs, including TFT, and proposed that GCV + TFT combination therapy may be an effective strategy to prevent the development of drug resistance.
Functional analysis, diversity, and distribution of the
ean
cluster responsible for 17
β
-estradiol degradation in sphingomonads
Authors: Zhang Mingliang , Gao Siyuan , Pan Kaihua , Liu Hongfei , Li Qian , Bai Xuekun , Zhu Qian , Chen Zeyou , Yan Xin , Hong Qing
Published: April 2024

17
β
-estradiol (E2) is a natural endocrine disruptor that is frequently detected in surface and groundwater sources, thereby threatening ecosystems and human health. The newly isolated E2-degrading strain
Sphingomonas colocasiae
C3-2 can degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway; the former is the primary pathway supporting the growth of this strain and the latter is a branching pathway. The novel gene cluster
ean
was found to be responsible for E2 degradation through the 4,5-seco pathway, where E2 is converted to estrone (E1) by EanA, which belongs to the short-chain dehydrogenases/reductases (SDR) superfamily. A three-component oxygenase system (including the P450 monooxygenase EanB1, the small iron-sulfur protein ferredoxin EanB2, and the ferredoxin reductase EanB3) was responsible for hydroxylating E1 to 4-hydroxyestrone (4-OH-E1). The enzymatic assay showed that the proportion of the three components is critical for its function. The dioxygenase EanC catalyzes ring A cleavage of 4-OH-E1, and the oxidoreductase EanD is responsible for the decarboxylation of the ring A-cleavage product of 4-OH-E1. EanR, a TetR family transcriptional regulator, acts as a transcriptional repressor of the
ean
cluster. The
ean
cluster was also found in other reported E2-degrading sphingomonads. In addition, the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1
via
the 9,10-seco pathway, but its encoding genes are not located within the
ean
cluster. These results refine research on genes involved in E2 degradation and enrich the understanding of the cleavages of ring A and ring B of E2.

IMPORTANCE

Steroid estrogens have been detected in diverse environments, ranging from oceans and rivers to soils and groundwater, posing serious risks to both human health and ecological safety. The United States National Toxicology Program and the World Health Organization have both classified estrogens as Group 1 carcinogens. Several model organisms (proteobacteria) have established the 4,5-seco pathway for estrogen degradation. In this study, the newly isolated
Sphingomonas colocasiae
C3-2 could degrade E2 through both the 4,5-seco pathway and the 9,10-seco pathway. The novel gene cluster
ean
(including
eanA
,
eanB1
,
eanC
, and
eanD
) responsible for E2 degradation by the 4,5-seco pathway was identified; the novel two-component monooxygenase EanE1E2 can open ring B of 4-OH-E1 through the 9,10-seco pathway. The TetR family transcriptional regulator EanR acts as a transcriptional repressor of the
ean
cluster. The cluster
ean
was also found to be present in other reported E2-degrading sphingomonads, indicating the ubiquity of the E2 metabolism in the environment.
A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection
Authors: Palmucci Julia R. , Sells Blake E. , Giamberardino Charles D. , Toffaletti Dena L. , Dai Baodi , Asfaw Yohannes G. , Dubois Laura G. , Li Zhong , Theriot Barbara , Schell Wiley A. , Hope William , Tenor Jennifer L. , Perfect John R.
Published: April 2024

Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of
Cryptococcus neoformans
and
Candida albicans
infection in combination with fluconazole—a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies. In this series of experiments, mice fed a ketogenic diet prior to infection with
C. neoformans
and treated with fluconazole had a significant decrease in fungal burden in both the brain (mean 2.66 ± 0.289 log
10
reduction) and lung (mean 1.72 ± 0.399 log
10
reduction) compared to fluconazole treatment on a conventional diet. During
C. albicans
infection, kidney fungal burden of mice in the keto-fluconazole combination group was significantly decreased compared to fluconazole alone (2.37 ± 0.770 log
10
-reduction). Along with higher concentrations of fluconazole in the plasma and brain tissue, fluconazole efficacy was maximized at a significantly lower concentration on a keto diet compared to a conventional diet, indicating a dramatic effect on fluconazole pharmacodynamics. Our findings indicate that a ketogenic diet potentiates the effect of fluconazole at multiple body sites during both
C. neoformans
and
C. albicans
infection and could have practical and promising treatment implications.

IMPORTANCE

Invasive fungal infections cause over 2.5 million deaths per year around the world. Treatments for fungal infections are limited, and there is a significant need to develop strategies to enhance antifungal efficacy, combat antifungal resistance, and mitigate treatment side effects. We determined that a high-fat, low-carbohydrate ketogenic diet significantly potentiated the therapeutic effect of fluconazole, which resulted in a substantial decrease in tissue fungal burden of both
C. neoformans
and
C. albicans
in experimental animal models. We believe this work is the first of its kind to demonstrate that diet can dramatically influence the treatment of fungal infections. These results highlight a novel strategy of antifungal drug enhancement and emphasize the need for future investigation into dietary effects on antifungal drug activity.
Late Triassic paleogeography of southern Laurentia and its fringing arcs: Insights from detrital zircon U-Pb geochronology and Hf isotope geochemistry, Auld Lang Syne basin (Nevada, USA)
Authors: Schwartz Theresa M. , Wyld Sandra J. , Colgan Joseph P. , Prihar Douglas W.
Published: April 2024

Fluvial strata of the Upper Triassic Chinle Formation and Dockum Group, exposed across the Western Interior of North America, have long been interpreted to record a transcontinental river system that connected the ancestral Ouachita orogen of Texas and Oklahoma, USA, to the Auld Lang Syne basin of northwestern Nevada, USA, its inferred marine terminus. Fluvial strata are well-characterized by existing detrital zircon data, but the provenance of the Auld Lang Syne basin is poorly constrained. We present new detrital zircon U-Pb and Hf isotopic data that characterize the provenance of Norian siliciclastic strata that dominate the Auld Lang Syne basin. Mixture modeling of Auld Lang Syne basin data identifies the Alleghany–Ouachita–Marathon belt of eastern Laurentia as a dominant source of sediment, but the presence of Triassic detrital zircon grains in Auld Lang Syne basin strata indicates that at least one peri-Laurentian arc segment had to have also contributed sediment. A comparison of new Hf isotopic data with those characterizing various peri-Laurentian volcanic arcs demonstrates that although multiple arc segments may have simultaneously contributed zircons to the Auld Lang Syne basin, the west Pangean arc of northern Mexico stands out as a unique source of highly evolved Permian to Triassic detrital zircon grains in samples from the Auld Lang Syne basin. Altogether, our data and analyses demonstrate source-to-sink connectivity between the Late Triassic (Norian) Cordilleran margin and remnant late Paleozoic highlands of southern to eastern Laurentia, which ultimately framed a Mississippi River–scale, transcontinental watershed that traversed the topographically subdued Laurentian continental interior.
An enhanced chemical maturation of juvenile arc crust recorded by the Urad Houqi intrusive suite in Langshan arc, Central Asia
Authors: Liu Min , Lai Shao-Cong , Ma Shuai , Zhang Fang-Yi , Zhu Ren-Zhi , Zhu Yu , Qin Jiang-Feng , Xu Bo , Yang Hang
Published: April 2024

Continental arc magmatism is crucial in producing juvenile continental crust of andesitic to dacitic composition, yet its impact on the formation of the modern mature continental crust, which is more enriched in potassic and granitic components, remains poorly understood. We examined a suite comprised of norite gabbro, gabbroic diorite, high-Mg diorite, dioritic enclave, and medium-K to high-K granites (the Urad Houqi suite) from the Langshan arc in the southern Central Asian Orogenic Belt (CAOB). Zircon U-Pb geochronology indicates that the Urad Houqi suite was formed ca. 278–268 Ma by a continuous magmatic event, marking the final episode of the late Paleozoic continental arc magmatism in the southern CAOB induced by the subduction of the Paleo-Asian Ocean. The suite exhibits a more potassic and fertile composition compared to typical continental arc magmas, and shows a continuous increasing K2O/Na2O ratio and incompatible element concentrations, including K, Rb, Th, and U, with increasing SiO2 content. The geochemical evolution of the suite offers valuable insights into the maturation process of the juvenile arc crust. By combining zircon Hf and bulk-rock Sr-Nd-Pb isotope studies, we demonstrated that the various lithologies within the Urad Houqi suite recorded a three-stage enhancement of the geochemical fertility of the juvenile Langshan arc crust: (1) generation of the initially fertile primary melt from the mantle wedge metasomatized by the recycled subducted sediments; (2) trans-crustal open-system hybridization processes, including peritectic reaction and magma mixing, that further fertilized the derived melts in addition to fractional crystallization; and (3) diverse petrogenetic processes that contributed to the fertility of the granitic magmas, including polybaric fractionation of the primary magma, anatexis of ancient crust, and extraction of high-silica melts from the shallow mush system. The three-stage maturation of the juvenile Langshan arc crust was typically coupled with the accelerated subduction of the Paleo-Asian Ocean since the earliest Permian. Our study finds that the Urad Houqi suite can serve as an example of modern continental crust maturation at continental arc settings.
Paediatric medication incident reporting: a multicentre comparison study of medication errors identified at audit, detected by staff and reported to an incident system
Authors: Li Ling , Badgery-Parker Tim , Merchant Alison , Fitzpatrick Erin , Raban Magdalena Z , Mumford Virginia , Metri Najwa-Joelle , Hibbert Peter Damian , Mccullagh Cheryl , Dickinson Michael , Westbrook Johanna I
Published: April 2024

Objectives

To compare medication errors identified at audit and via direct observation with medication errors reported to an incident reporting system at paediatric hospitals and to investigate differences in types and severity of errors detected and reported by staff.

Methods

This is a comparison study at two tertiary referral paediatric hospitals between 2016 and 2020 in Australia. Prescribing errors were identified from a medication chart audit of 7785 patient records. Medication administration errors were identified from a prospective direct observational study of 5137 medication administration doses to 1530 patients. Medication errors reported to the hospitals’ incident reporting system were identified and matched with errors identified at audit and observation.

Results

Of 11 302 clinical prescribing errors identified at audit, 3.2 per 1000 errors (95% CI 2.3 to 4.4, n=36) had an incident report. Of 2224 potentially serious prescribing errors from audit, 26.1% (95% CI 24.3 to 27.9, n=580) were detected by staff and 11.2 per 1000 errors (95% CI 7.6 to 16.5, n=25) were reported to the incident system. Although the prescribing error detection rates varied between the two hospitals, there was no difference in incident reporting rates regardless of error severity. Of 40 errors associated with actual patient harm, only 7 (17.5%; 95% CI 8.7% to 31.9%) were detected by staff and 4 (10.0%; 95% CI 4.0% to 23.1%) had an incident report. None of the 2883 clinical medication administration errors observed, including 903 potentially serious errors and 144 errors associated with actual patient harm, had incident reports.

Conclusion

Incident reporting data do not provide an accurate reflection of medication errors and related harm to children in hospitals. Failure to detect medication errors is likely to be a significant contributor to low error reporting rates. In an era of electronic health records, new automated approaches to monitor medication safety should be pursued to provide real-time monitoring.
Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer
Authors: Zhang Feifei , Sahu Varun , Peng Ke , Wang Yichen , Li Tianxia , Bala Pratyusha , Aitymbayev Daulet , Sahgal Pranshu , Schaefer Antje , Der Channing J , Ryeom Sandra , Yoon Sam , Sethi Nilay , Bass Adam J , Zhang Haisheng
Published: April 2024

Objective

Genomic studies of gastric cancer have identified highly recurrent genomic alterations impacting RHO signalling, especially in the diffuse gastric cancer (DGC) histological subtype. Among these alterations are interchromosomal translations leading to the fusion of the adhesion protein CLDN18 and RHO regulator ARHGAP26. It remains unclear how these fusion constructs impact the activity of the RHO pathway and what is their broader impact on gastric cancer development. Herein, we developed a model to allow us to study the function of this fusion protein in the pathogenesis of DGC and to identify potential therapeutic targets for DGC tumours with these alterations.

Design

We built a transgenic mouse model with
LSL-CLDN18-ARHGAP26
fusion engineered into the
Col1A1
locus where its expression can be induced by Cre recombinase. Using organoids generated from this model, we evaluated its oncogenic activity and the biochemical effects of the fusion protein on the RHOA pathway and its downstream cell biological effects in the pathogenesis of DGC.

Results

We demonstrated that induction of
CLDN18-ARHGAP26
expression in gastric organoids induced the formation of signet ring cells, characteristic features of DGC and was able to cooperatively transform gastric cells when combined with the loss of the tumour suppressor gene
Trp53. CLDN18-ARHGAP26
promotes the activation of RHOA and downstream effector signalling. Molecularly, the fusion promotes activation of the focal adhesion kinase (FAK) and induction of the YAP pathway. A combination of FAK and YAP/TEAD inhibition can significantly block tumour growth.

Conclusion

These results indicate that the
CLDN18-ARHGAP26
fusion is a gain-of-function DGC oncogene that leads to activation of RHOA and activation of FAK and YAP signalling. These results argue for further evaluation of emerging FAK and YAP-TEAD inhibitors for these deadly cancers.
Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis
Authors: Liu Jinxia , MacNaughtan Jane , Kerbert Annarein J C , Portlock Theo , Martínez Gonzalez Javier , Jin Yi , Clasen Frederick , Habtesion Abeba , Ji Huoyan , Jin Qin , Phillips Alexandra , De Chiara Francesco , Ingavle Ganesh , Jimenez Cesar , Zaccherini Giacomo , Husi Katherine , Rodriguez Gandia Miguel Angel , Cordero Paul , Soeda Junpei , McConaghy Lynda , Oben Jude , Church Karen , Li Jia V , Wu Haifeng , Jalan Aarti , Gines Pere , Solà Elsa , Eaton Simon , Morgan Carrie , Kowalski Michal , Green Daniel , Gander Amir , Edwards Lindsey A , Cox I Jane , Cortez-Pinto Helena , Avery Thomas , Wiest Reiner , Durand Francois , Caraceni Paolo , Elosua Roberto , Vila Joan , Pavesi Marco , Arroyo Vicente , Davies Nathan , Mookerjee Rajeshwar P , Vargas Victor , Sandeman Susan , Mehta Gautam , Shoaie Saeed , Marchesi Julian , Albillos Agustín , Andreola Fausto , Jalan Rajiv
Published: April 2024

Objective

Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis.

Design

Performance of Yaq-001 was evaluated
in vitro
. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed.

Results

Yaq-001 exhibited rapid adsorption kinetics for endotoxin.
In vivo
, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial.

Conclusions

This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation.

Trial registration number

NCT03202498
.
Decreased pancreatic amylase activity after acute high-intensity exercise and its effects on post-exercise muscle glycogen recovery
Authors: Kondo Saki , Karasawa Takuya , Koike Atsuko , Tsutsui Momoko , Kunisawa Jun , Terada Shin
Published: April 2024

Our prior results showed that an acute bout of endurance exercise for 6 h, but not 1 h, decreased pancreatic amylase activity, indicating that acute endurance exercise may affect carbohydrate digestive capacity in an exercise duration-dependent manner. Here, we investigated the effects of acute endurance exercise of different intensities on mouse pancreatic amylase activity. Male C57BL/6J mice performed low- or high-intensity running exercise for 60 min at either 10 (Ex-Low group) or 20 m/min (Ex-High group). The control group comprised sedentary mice. Immediately after acute exercise, pancreatic amylase activity was significantly decreased in the Ex-High group and not the Ex-Low group in comparison with the control group. To determine whether the decreased amylase activity induced by high-intensity exercise influenced muscle glycogen recovery after exercise, we investigated the rates of muscle glycogen resynthesis in Ex-High group mice administered either oral glucose or starch solution (2.0 mg/g body weight) immediately after exercise. The starch-fed mice exhibited significantly lower post-exercise glycogen accumulation rates in the 2-h recovery period compared with the glucose-fed mice. This difference in the glycogen accumulation rate was absent for starch- and glucose-fed mice in the sedentary (no exercise) control group. Furthermore, the plasma glucose AUC during early post-exercise recovery (0–60 min) was significantly lower in the starch-fed mice than in the glucose-fed mice. Thus, our findings suggest that acute endurance exercise diminishes the carbohydrate digestive capacity of the pancreas in a manner dependent on exercise intensity, with polysaccharides leading to delayed muscle glycogen recovery after exercise.
Constructing Pavement Roughness of a Three-Dimensional Bridge in Abaqus for Vehicle Scanning Method
Authors: Yang Judy P. , Jiang Han-Cyuan
Published: April 2024

In this study, a procedure for constructing pavement roughness in a three-dimensional bridge subjected to a vehicle using Abaqus is proposed for numerical simulation of vehicle–bridge interaction problems. As the plug-in RufGen, a graphical user interface in Abaqus/CAE for surface interaction, creates a hexahedron with a rough surface and attaches it to the bridge deck, the resulting weight of a bridge model can be much larger than the original one. In the vehicle scanning method, it is essential to keep a finite element bridge model with an unchanged weight after imposing a rough surface on it in consideration of the roughness effect for bridge health monitoring. As such, the proposed procedure is aimed at resolving this issue, with the following two highlights: First, the Toeplitz matrix is introduced to generate a rough surface in three dimensions to ensure the randomness of roughness in the two perpendicular directions under a given roughness profile. Second, a shell-type rough pavement is established for directly using as the bridge pavement or attaching to the bridge deck, which minimizes weight increment in the bridge.
A Method for Analyzing the Operating Data of Electric Energy Meters Based on Data Mining Analysis
Authors: Chencheng Wang , Lijuan Pu , Zhihui Zhao , Jiefu Zhang
Published: April 2024

Aiming at the problem of error estimation of smart meters in distribution network, a method of error estimation of smart meters based on particle swarm optimization convolutional neural network is proposed. This method establishes an intelligent energy meter error estimation model through data collection, data prediction, and preprocessing. To address the convergence issue in training, the interlayer distribution of weights is adjusted to improve training quality. This method fully utilizes template calibration information to transform indicator detection under complex conditions into simple and effective isometric segmentation, transforming label recognition from complex text detection and recognition tasks to simple and efficient binary detection tasks, with better robustness. The effectiveness and high robustness of the proposed method have been demonstrated through experimental verification.