bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors predicting slow visual recovery following microkeratome‐assisted myopic LASIK
Authors: Safir Margarita , Sorkin Nir , Kaiserman Igor , Sela Tzahi , Munzer Gur , Spierer Oriel , Mimouni Michael
Published: September 2024

Purpose

To identify factors predicting slow visual recovery following myopic microkeratome assisted in situ keratomileusis (LASIK).

Design

Retrospective study.

Methods

This study included consecutive patients who underwent microkeratome‐assisted myopic LASIK between January 2005 and December 2019 at Care Vision Laser Center, Tel Aviv, Israel. Patients were divided into three groups according to whether they experienced normal recovery of visual acuity (1 week visit), slow visual recovery (1 month visit) or very slow recovery (>1 month). Normal visual recovery was defined as achieving an efficacy index of 0.9 or greater. Efficacy index was calculated as postoperative uncorrected visual acuity/preoperative best corrected visual acuity. A comparison of baseline and intraoperative parameters was performed.

Results

Overall, 10 439 eyes were included. Mean age was 30.8 ± 8.7 years and 47.1% were females. The slower visual recovery groups (slow 11.4%, n = 1191; very slow 8.4%, n = 875) were of older age (p < 0.001), steeper preoperative steep keratometry (p = 0.002) and larger refractive astigmatism (p < 0.001). In binary logistic regression older age (p < 0.001), female gender (p = 0.001), larger astigmatism (p < 0.001) and high myopia (p < 0.001) remained significant predictors of slow visual recovery.

Conclusion

Slow visual recovery was observed in 19.8% of patients following myopic LASIK. Older age, female gender, larger astigmatism and high myopia were associated with slow visual recovery. Patients may be advised accordingly.
Do sustainable savings decisions through deposits and shares by members influence the choice of financial cooperatives?
Authors: Kamau Juliana N. , Mathuva David M. , Ndiritu S. Wagura
Published: September 2024

The study investigates whether the choice of a financial cooperative is influenced by sustainable savings decisions through deposits or shares. The moderating influence of digital financial services (DFS) and an individual's reason for joining a financial cooperative are also investigated. Data are gathered from a cross‐sectional sample of 334 respondents drawn from 86 savings and credit cooperative societies (Saccos) in Kenya. The final sample comprises of 46 deposit‐taking (220 respondents) and 40 non–deposit‐taking (114 respondents) Saccos. Two‐sample tests, correlation and logistic regression analyses are performed to establish the factors influencing Sacco choice. Consistent with the mutual incentives and lifecycle theories, the findings reveal that an individual's choice of a financial cooperative is influenced by individual, as well as socio‐economic and environmental factors. The study finds that the desire to mobilize sustainable deposits is a more important consideration compared to building shares when choosing a Sacco. We further find that DFS are important in choosing a Sacco owing to the increased engagement and transparency associated with them. Other factors influencing Sacco choice include marital status, income levels and household location. The results help inform the focus by Sacco managers, regulators and policy makers in terms of the growth incentives to consider.
Government dishonesty, trust and cooperative behaviour: Evidence from China's Great Leap Forward
Authors: Qiliang Mao , Shanming Gou
Published: September 2024

This paper explores the long‐term impact of China's Great Leap Forward (GLF) on current differences in cooperative behaviour across Chinese regions and the underlying trust channel of causality. Combining the current firm‐level survey with grain yield over‐reporting during the GLF era, we find that past government dishonesty regarding over‐reporting in the GLF period has long‐term negative consequences on people's behaviours. The firms in the prefecture with a higher degree of yield over‐reporting are less likely to engage in R&D collaborations today. Further tests reveal the possible trust channel through which past government dishonesty impedes current cooperative behaviour. We extend the analyses to social norms of trust and show that GLF over‐reporting has shifted an individual's internal norms towards a present‐day mistrust culture, which contributes to explain the negative effect of GLF over‐reporting on cooperative behaviour. Our findings suggest that dishonest behaviours by local governments in the past can lead to lasting adverse effects on an individual's behaviour in the form of mistrust and subsequent lower frequencies of cooperative behaviour, providing new insights on the origins of cultural differences and human behaviours by investigating the role of governments in shaping social and economic interactions.
Isovaleramide attenuates ethylene glycol poisoning‐induced acute kidney injury and reduces mortality by inhibiting alcohol dehydrogenase activity in rats
Authors: Yang Kai , Zhang Xiaoxia , Yang Jianzhong , Huojiahemaiti Xiaokelaiti , Li Xinpeng , Liu Ziyang , Peng Peng
Published: September 2024

We explored the potential value of the alcohol dehydrogenase (ADH) inhibitor isovaleramide (ISO) in the treatment of acute ethylene glycol (EG) poisoning‐induced acute kidney injury. Sprague–Dawley rats were divided into the control, EG, EG + ISO (10 mg/kg) and EG + ISO (20 mg/kg) groups. It is found that ISO intervention significantly reduced the ADH activity in liver tissue by using visible spectrophotometry, inhibited the in vivo metabolism of EG by using gas chromatography, lowered the levels of toxic metabolites glycolic acid and oxalic acid by using high‐performance liquid chromatography and decreased the expression of kidney injury markers serum creatinine (sCr), KIM‐1, neutrophil gelatinase‐associated lipocalin (NGAL) and liver fatty acid‐binding protein (L‐FABP) by ELISA. Additionally, Western blotting results showed that ISO down‐regulated the expression of apoptotic factors Bax and cleaved caspase‐3 in the kidneys and upregulated the expression of antiapoptotic factor Bcl‐2. Pizzolato staining and polarized light microscopy results revealed the reduced deposition of calcium oxalate crystals in the kidney tubules. Using haematoxylin and eosin (H&E), periodic acid‐Schiff (PAS) and Masson staining, we found attenuated kidney tissue pathological injury. Finally, ISO significantly reduced the mortality rate. In conclusion, ISO has the potential to be a valuable drug for the treatment of EG poisoning‐induced acute kidney injury.
Real‐world outcomes for high‐risk non‐muscle‐invasive bladder cancer: screened patients for the BRAVO trial
Authors: Conroy Samantha , Jubber Ibrahim , Noon Aidan P. , Rosario Derek J. , Griffin Jon , Morgan Susan , Hubbard Rachel , Kennish Steve , Mitchell Stephen , Venugopal Suresh , Linton Kate , Rajasundaram Ramanan , Hussain Syed A. , Catto James W.F.
Published: September 2024

Objective

To report real‐world outcomes for high‐risk non‐muscle‐invasive bladder cancer (HRNMIBC), including bacillus Calmette‐Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible.

Methods

We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case‐note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer‐specific survival.

Results and limitations

A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) ‘other’ treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All‐cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5–42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35–5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3–0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17–3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19–36.25) months. In multivariable analysis, BC‐specific mortality was more common in older patients (HR 4.87, 95% CI 1.1–21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23–4.16; P = 0.008) but did not vary with initial treatment.

Conclusions

Patients with HRNMIBC are at high‐risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection.
Microclimate buffering by epiphytes reduces climate overlap across elevations
Authors: Soifer Lydia G. , Scheffers Brett R.
Published: September 2024

Thermal variation over space and time shapes global patterns of biodiversity and responses of species to climate change. Vertical microclimate gradients from the understory to the canopy mediate biogeographic patterns of arboreal species across larger spatial scales. Yet, the magnitude to which microhabitats in the canopy, such as large epiphytes, alter the exposure of arboreal species to hot and variable canopy conditions across biogeographic gradients is not well known. We first examine the extent to which maximum temperatures and temperature variation in epiphytic bird's nest ferns (BNFs) and the understory are lower than those in the canopy across an elevation gradient in the Philippines and the environmental factors influencing these differences. We find that differences in maximum temperatures (i.e., offset) and temperature variation (i.e., buffering) between the canopy and BNFs are greater than differences between the canopy and understory. Offset and buffering are largest when canopy temperatures are high and are positively impacted by precipitation. Furthermore, we address the theory that exposure to higher thermal variation in the canopy may increase the range sizes of arboreal species. We find that lower thermal variation over time in BNFs reduces the thermal overlap between low and high elevations relative to canopy temperatures. Arboreal species that shelter in BNFs during the day may therefore have narrow physiological tolerances and consequently smaller elevational ranges. By providing thermal regimes more similar to the understory than the canopy, BNFs may therefore effectively function as “arboreal soil”, mediating impacts of arboreality on patterns of biodiversity and trait variation.
Bridging the gap: Linking prototyping and technology readiness levels for integrative product development
Authors: Rehberg Laura , Brem Alexander
Published: September 2024

Shorter development cycles, increasing complexity due to the interaction of hardware and software and the simultaneous pressure to innovate and reduce costs lead to products being launched early that have not yet been sufficiently validated and tested. The prototyping phase is crucial to ensure maturity as a preliminary stage to series production. Although this validation is critical to ensure the maturity of the product or technology to avoid recalls, previous research has focused on exploring the phenomenon of prototyping in general. To fill this gap, we use the standardized framework of technology readiness levels and develop prototyping readiness levels that allow for a graded assessment of maturity.

Our empirical study is based on the unique case of the Boeing 737 Max 8 and a research project to develop an automated prototyping hub. Our findings show how mismanagement of prototypes and inadequate technology readiness level (TRL) assessment can lead to serious safety issues. Based on these findings, we introduce prototyping readiness levels that complement the idea of TRLs to reduce and eliminate bottlenecks and errors in the early stages of the development process.
Anti‐tissue factor antibody conjugated with monomethyl auristatin E or deruxtecan in pancreatic cancer models
Authors: Tsumura Ryo , Anzai Takahiro , Koga Yoshikatsu , Takashima Hiroki , Matsumura Yasuhiro , Yasunaga Masahiro
Published: September 2024

Antibody–drug conjugates (ADCs) have been recognized as a promising class of cancer therapeutics. Tissue factor (TF), an initiator of the blood coagulation pathway, has been investigated regarding its relationship with cancer, and several preclinical and clinical studies have presented data on anti‐TF ADCs, including tisotumab vedotin, which was approved in 2021. However, the feasibility of other payloads in the design of anti‐TF ADCs is still unclear because no reports have compared payloads with different cytotoxic mechanisms. For ADCs targeting other antigens, such as Her2, optimizing the payload is also an important issue in order to improve in vivo efficacy. In this study, we prepared humanized anti‐TF Ab (clone.1084) conjugated with monomethyl auristatin E (MMAE) or deruxtecan (DXd), and evaluated the efficacy in several cell line‐ and patient‐derived xenograft models of pancreatic cancer. As a result, optimizing the drug / Ab ratio was necessary for each payload in order to prevent pharmacokinetic deterioration and maximize delivery efficiency. In addition, MMAE‐conjugated anti‐TF ADC showed higher antitumor effects in tumors with strong and homogeneous TF expression, while DXd‐conjugated anti‐TF ADC was more effective in tumors with weak and heterogeneous TF expression. Analysis of a pancreatic cancer tissue array showed weak and heterogeneous TF expression in most TF‐positive specimens, indicating that the response rate to pancreatic cancer might be higher for DXd‐ than MMAE‐conjugated anti‐TF ADC. Nevertheless, our findings indicated that optimizing the ADC payloads individually in each patient could maximize the potential of ADC therapeutics.
The nature and development of cognitive offloading in children
Authors: Armitage Kristy L. , Gilbert Sam J.
Published: September 2024

Humans routinely use external thinking tools, like pencil and paper, maps, and calculators, to solve cognitive problems that would have once been solved internally. As many youth face unprecedented exposure to increasingly capable technological aids, there is a growing pressure to understand children's cognitive offloading capacities and propensities, and what they stand to gain or lose as frequent offloaders in the modern world. In this article, we review emerging research on the development of cognitive offloading. Children as young as 4 years can engage in effective offloading strategies that follow principles similar to those used by adults—for example, greater recruitment of external support when tasks are more difficult. However, young children's strategies also show evidence of bias (sometimes inadequate and sometimes excessive offloading), lack of selectivity, and lack of self‐initiation. We also draw attention to important avenues for future research, working toward protecting and nurturing children's cognitive well‐being in the digital age.
A Particle‐Based Approach to Extract Dynamic 3D FTLE Ridge Geometry
Authors: Stelter Daniel , Wilde Thomas , Rössl Christian , Theisel Holger
Published: September 2024

Lagrangian coherent structures (LCS) is an important concept for the visualization of unsteady flows. They describe the boundaries of regions for which material transport stays mostly coherent over time which can help for a better understanding of dynamical systems. One of the most common techniques for their computation is the extraction of ridges from the finite‐time Lyapunov exponent (FTLE) field. FTLE ridges are challenging to extract, both in terms of accuracy and performance, because they expose strong gradients of the underlying field, tend to come close to each other and are dynamic with respect to different time parameters. We present a new method for extracting FTLE ridges for series of integration times which is able to show how coherent regions and their borders evolve over time. Our techniques mainly build on a particle system which is used for sampling the ridges uniformly. This system is highly optimized for the challenges of FTLE ridge extraction. Further, it is able to take advantage of the continuous evolvement of the ridges which makes their sampling for multiple integration times much faster. We test our method on multiple 3D datasets and compare it to the standard Marching Ridges technique. For the extraction examples our method is 13 to over 300 times faster, suggesting a significant advantage.
Decision regret following surgical management of pilonidal disease
Authors: Banks J. , Lee E. , Lee M. J. , Brown S. R. ,   PITSTOP Management Group
Published: September 2024

Aim

Surgical decision making in the context of pilonidal disease (PD) can be challenging. Current evidence for the management of PD is inadequate and optimum treatment is not clear. This paper reports on patient experience of shared decision making (SDM) and decision regret following surgical management of PD.

Method

The Pilonidal Trial. Studying the Treatment Options (PITSTOP) study (ISRCTN95551898) is a prospective cohort study of patients with PD treated between May 2019 and March 2022. This subanalysis reports the results of quantitative data capture between baseline and 6 months post‐procedure. Baseline data consisted of patient and disease characteristics, surgical procedure and impression of SDM. Post‐procedure data consisted of operative outcomes and decision regret. Multiple linear regression analysis was used to analyse the relationship between clinical outcomes and decision regret.

Results

Overall, 677 patients were included, and follow‐up data to 6 months were available for 476 (71%). Most (59.5%) patients underwent major excisional surgery; 45.1% of patients experienced a postoperative complication. Participant impression of SDM was positive, with a median CollaboRATE mean‐score response of 3 (interquartile range: 3–4). Of the patients who underwent a ‘leave open’ approach, 20.6% were dissatisfied or very dissatisfied with their treatment. Postoperative complications (β = 3.21, 95% CI: −12.75 to 7.25, p < 0.001) and disease recurrence (β = 11.5, 95% CI: −10.6 to 9.4, p < 0.001) were both associated with higher rates of decision regret.

Conclusion

The clinical outcomes, postoperative complications and recurrence, were associated with higher levels of decision regret. Surgeons treating patients with PD should practice SDM and ensure that patient priorities inform treatment approach.
Subclinical Pancreas Rejection on Protocol Biopsy Within the First Year of Simultaneous Pancreas Kidney Transplant
Authors: Budhiraja Pooja , Heilman Raymond L. , Butterfield Richard , Reddy Kunam S. , Khamash Hassan A. , Abu Jawdeh Bassam G. , Jadlowiec Caroline C. , Katariya Nitin , Smith Maxwell , Jaramillo Andres , Alajous Salah , Mathur Amit , Hacke Katrin , Chakkera Harini A.
Published: September 2024

This single‐center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post‐transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24–24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.
Noninvasive skin swab analysis detects environmental drug exposure of pharmacy staff
Authors: Thompson Samantha , Abelyan Samvel , Panitchpakdi Morgan , Zemlin Jasmine , Thomas Sydney , Zhao Haoqi Nina , Dorrestein Pieter C. , Tsunoda Shirley M.
Published: September 2024

The skin is complex with multiple layers serving protective, regulatory, and detective functions. The skin hosts chemicals originating from consumption, synthesis, and the environment. Skin chemicals can provide insight into one's daily routine or their level of safety in a work environment. The goal of this study was to investigate the utility of noninvasive skin swabs to detect drugs in a pharmacy setting and to determine whether drugs are transferred to the skin of pharmacy staff. To answer this question, skin swabs were collected from healthy pharmacy staff workers and healthy non‐pharmacy individuals and analyzed via untargeted liquid chromatography–tandem mass spectrometry (LC–MS/MS). Drugs were annotated through library matching against the GNPS community spectral library. We then used questionnaire data to exclude medications that participants took orally or applied topically and focused on the drugs participants were exposed to in the work setting. Overall, pharmacy staff had a higher number and variety of medications on their skin as compared with healthy individuals who did not work in a pharmacy. In addition, we identified some chemicals such as N,N‐Diethyl‐metatoluamide on a large number of subjects in both experimental and control groups, indicating environmental exposure to this compound may be ubiquitous and long‐lasting.
The Contribution of Teacher Self‐Efficacy, Resilience and Emotion Regulation to Teachers' Well‐Being: Technology‐Enhanced Teaching Context
Authors: Lu Lihua , Wang Cuiying , Wang Yunsong
Published: September 2024

The COVID‐19 pandemic has significantly altered teaching methodologies by integrating technology into syllabi, emphasising the crucial role of teacher well‐being influenced by positive psychology. Also, as the foremost issues of education, teachers’ individual factors should be considered as their beliefs in their capabilities to persist in the case of difficulties and their emotion regulation (ER) have been underlined in the literature. Therefore, this study examined the correlation between teacher self‐efficacy (TSE), resilience and ER and teacher well‐being among 424 Chinese teachers. The findings through running the structural equation model revealed that those teachers with a heightened degree of TSE, resilience and ER are more likely to have better well‐being. Multiple regression analysis indicated that TSE explained 61% of the variance in teachers’ well‐being. Meanwhile, the same analysis found that resilience and ER explained 54% and 51% of the variance in teachers’ well‐being, respectively. Succinctly, some educational implications are provided for educational members to attract their attention to the role of these constructs in technology‐enhanced teaching.
A Sex‐Specific Trade‐Off Between Pesticide Resistance and Tolerance to Heat‐Induced Sterility in Tetranychus urticae
Authors: Costa Sofia G. , Magalhães Sara , Santos Inês , Zélé Flore , Rodrigues Leonor R.
Published: September 2024

Current pest management relies extensively on pesticide application worldwide, despite the frequent rise of pesticide resistance in crop pests. This is particularly worrisome because resistance is often not costly enough to be lost in populations after pesticide application, resulting in increased dependency on pesticide application. As climate warming increases, effort should be put into understanding how heat tolerance will affect the persistence of pesticide resistance in populations. To address this, we measured heat tolerance in two populations of the spider mite crop pest Tetranychus urticae that differ in the presence or absence of a target‐site mutation conferring resistance to etoxazole pesticide. We found that developmental time and fertility, but not survival, were negatively affected by increasing temperatures in the susceptible population. Furthermore, we found no difference between resistant and susceptible populations in all life‐history traits when both sexes developed at control temperature, nor when females developed at high temperature. Resistant heat‐stressed males, in contrast, showed lower fertility than susceptible ones, indicating a sex‐specific trade‐off between heat tolerance and pesticide resistance. This suggests that global warming could lead to reduced pesticide resistance in natural populations. However, resistant females, being as affected by high temperature as susceptible individuals, may buffer the toll in resistant male fertility, and the shorter developmental time at high temperatures may accelerate adaptation to temperature, the pesticide or the cost thereof. Ultimately, the complex dynamic between these two factors will determine whether resistant populations can persist under climate warming.
Carpometacarpal joint arthrodesis to treat a luxation of the fourth carpal bone in a filly
Authors: Charbonnel Anna , Meurice Antoine , de Fourmestraux Claire
Published: September 2024

A 1‐month‐old Paint filly was diagnosed with a latero‐distal luxation of the fourth carpal bone associated with avulsion fractures of the third and fourth carpal bones and rupture of intercarpal ligaments based on clinical, radiography and computed tomography examination. A carpometacarpal (CMC) joint arthrodesis was performed using a lateral 3.5 mm 5‐hole Locking Compression Plate (LCP) T‐plate and a medial 3.5 mm 5‐hole narrow LCP plate associated with mediocarpal arthroscopic exploration. An external coaptation was maintained for 6 weeks. No complication was reported and the filly was full loading the day after surgery. Radiographical follow‐up was available 6 and 14 weeks after surgery showing an intact construct and stable fixation with a complete fusion of the lateral part of the carpometacarpal joint at 14 weeks postoperatively. The filly was sound on pasture without angular deformity 4 months after surgery. Luxation of the fourth carpal bone was successfully stabilised using two LCP plates, leading to complete soundness and preservation of middle carpal joint motion.
Prediction of stock prices with automated reinforced learning algorithms
Authors: Yasin Said , Paschke Adrian , Al Qundus Jamal
Published: September 2024

Predicting stock price movements remains a major challenge in time series analysis. Despite extensive research on various machine learning techniques, few models have consistently achieved success in automated stock trading. One of the main challenges in stock price forecasting is that the optimal model changes over time due to market dynamics. This paper aims to predict stock prices using automated reinforcement learning algorithms and to analyse their efficiency compared with conventional methods. We automate DQN models and their variants, known for their adaptability, by continuously retraining them using recent data to capture market dynamics. We demonstrate that our dynamic models improve the accuracy of predicting the directions of various DAX stocks from 50.00% to approximately 60.00%, compared with conventional methods. Additionally, we conclude that dynamic models should be updated in response to shifts rather than at fixed intervals.
The AXL inhibitor bemcentinib overcomes microenvironment‐mediated resistance to pioglitazone in acute myeloid leukemia
Authors: Zhu Jaja , Guérineau Hippolyte , Lefebvre‐Fortané Anne‐Margaux , Largeaud Laetitia , Lambert Juliette , Rousselot Philippe , Boudouin Maèva , Calvo Julien , Prost Stéphane , Clauser Sylvain , Bardet Valérie
Published: September 2024

Prognosis of acute myeloid leukemia (AML) remains poor especially in older patients who are ineligible for standard chemotherapy or have refractory disease. Here, we study the potential of Peroxisome Proliferator‐Activated Receptor (PPAR)‐γ agonist pioglitazone to improve the treatment of AML. We show that pioglitazone exerts an anti‐proliferative and anti‐clonogenic effect on AML cell lines KG‐1a, MOLM‐14 and OCI‐AML3 and on primary cultures from AML patients. However, co‐culture of AML cells with stromal cells mimicking the bone marrow microenvironment counteracts this effect, suggesting the existence of a stroma‐mediated resistance mechanism to pioglitazone. We show that pioglitazone treatment upregulates the receptor AXL in AML cells at the mRNA and protein level, allowing AXL to be phosphorylated by its ligand Gas6, which is secreted by the stroma. Addition of exogenous Gas6 or stromal cell conditioned medium also abolishes the anti‐proliferative effect of pioglitazone, with an increase in AXL phosphorylation observed in both conditions. Co‐incubation with the AXL inhibitor bemcentinib restored the anti‐leukemic activity of pioglitazone in the presence of stromal cells by reducing AXL phosphorylation to its baseline level. We also confirm that this resistance mechanism is PPAR‐γ‐dependent as stromal cells invalidated for PPAR‐γ are unable to inhibit the antileukemic effect of pioglitazone. Altogether, we suggest that pioglitazone treatment exerts an anti‐leukemic effect but concomitantly triggers a stroma‐mediated resistance mechanism involving the Gas6/AXL axis. We demonstrate that a combination of pioglitazone with an AXL inhibitor overcomes this mechanism in primary cultures and AML cell lines and exerts potent anti‐leukemic activity requiring further evaluation in vivo through murine xenograft pre‐clinical models.
Senescence in the ageing skin: a new focus on mTORC1 and the lysosome
Authors: Smith Phineas , Carroll Bernadette
Published: September 2024

Ageing is defined as the progressive loss of tissue function and regenerative capacity and is caused by both intrinsic factors i.e. the natural accumulation of damage, and extrinsic factors i.e. damage from environmental stressors. Cellular senescence, in brief, is an irreversible exit from the cell cycle that occurs primarily in response to excessive cellular damage, such as from ultraviolet (UV) exposure and oxidative stress, and it has been comprehensively demonstrated to contribute to tissue and organismal ageing. In this review, we will focus on the skin, an organ which acts as an essential protective barrier against injury, insults, and infection. We will explore the evidence for the existence and contribution of cellular senescence to skin ageing. We discuss the known molecular mechanisms driving senescence in the skin, with a focus on the dysregulation of the master growth regulator, mechanistic Target of Rapamycin Complex 1 (mTORC1). We explore the interplay of dysregulated mTORC1 with lysosomes and how they contribute to senescence phenotypes.
Zero‐beta risks and required returns: ESG and CAPM
Authors: Johnstone David , Grant Andrew
Published: September 2024

We ask how idiosyncratic zero‐beta risks (e.g., the risk of litigation or R&D failing) affect the firm's cost of capital under capital asset pricing model (CAPM). Surprisingly, perhaps, CAPM theory reveals that adding an idiosyncratic risk to the firm's payoff distribution will usually although not necessarily increase the firm's cost of capital. Lintner's famous original CAPM expositions revealed that the firm's CAPM cost of capital is a function of the ratio of the covariance of its cash payoff with the market to its payoff mean. Lintner proved that an idiosyncratic risk that affects the firm's payoff covarianceper unit of meanis“priced” in the sense that it necessarily alters the firm's CAPM discount rate. We explain and clarify Lintner's argument using elementary CAPM equations and numerical examples.
Examining beginner Spanish learners' interactions during text chat: Self‐monitoring and the impact of metacognitive instruction
Authors: Moranski Kara , Ziegler Nicole , Finnegan Abbie
Published: September 2024

Text chat facilitates L2 use by providing learners with extended time to plan, monitor, and process production during interactional tasks. However, learners may not naturally take advantage of these affordances, especially for providing peer feedback. This study used video‐enhanced chat scripts to examine the behavior of beginner L2 Spanish learners (n = 46) completing decision‐consensus tasks via text chat, investigating how learners interacted with the medium to self‐monitor by deleting text before sending. Learners were also differentially assigned to receive metacognitive instruction (MI) to learn ways to provide corrective feedback to peers or engage in language‐related episodes (LREs). Results showed that all learners frequently used text chat's affordances to self‐correct and also integrated technology to resolve LREs (creating technology‐assisted LREs). However, MI did not have a significant impact on the production of corrective feedback or LREs, potentially due to attentional resources expended during self‐correction. These findings suggest that completing task‐based activities within text chat may be beneficial for promoting beginner learners' linguistic processing and integrating technology to facilitate discussion of L2 form but less impactful for promoting peer feedback.
Eddy covariance measurements reveal a decreased carbon sequestration strength 2010–2022 in an African semiarid savanna
Authors: Wieckowski Aleksander , Vestin Patrik , Ardö Jonas , Roupsard Olivier , Ndiaye Ousmane , Diatta Ousmane , Ba Seydina , Agbohessou Yélognissè , Fensholt Rasmus , Verbruggen Wim , Gebremedhn Haftay Hailu , Tagesson Torbern
Published: September 2024

Monitoring the changes of ecosystem functioning is pivotal for understanding the global carbon cycle. Despite its size and contribution to the global carbon cycle, Africa is largely understudied in regard to ongoing changes of its ecosystem functioning and their responses to climate change. One of the reasons is the lack of long‐term in situ data. Here, we use eddy covariance to quantify the net ecosystem exchange (NEE) and its components—gross primary production (GPP) and ecosystem respiration (Reco) for years 2010–2022 for a Sahelian semiarid savanna to study trends in the fluxes. Significant negative trends were found for NEE (12.7 ± 2.8 g C m2 year−1), GPP (39.6 ± 7.9 g C m2 year−1), and Reco (32.2 ± 8.9 g C m2 year−1). We found that NEE decreased by 60% over the study period, and this decrease was mainly caused by stronger negative trends in rainy season GPP than in Reco. Additionally, we observed strong increasing trends in vapor pressure deficit, but no trends in rainfall or soil water content. Thus, a proposed explanation for the decrease in carbon sink strength is increasing atmospheric dryness. The warming climate in the Sahel, coupled with increasing evaporative demand, may thus lead to decreased GPP levels across this biome, and lowering its CO2 sequestration.
Ubrogepant users' real‐world experience: Patients on ubrogepant, characteristics and outcomes (UNIVERSE) study
Authors: Shewale Anand R. , Poh Weijie , Reed Michael L. , Liu Jinjie , Cadiou Francois , Ezzati Ali , Burslem Kate , Manthena Shivaji , Lipton Richard B.
Published: September 2024

Objective

To assess the real‐world effectiveness of ubrogepant by evaluating self‐reported satisfaction with pain relief, ability to think clearly, and return to normal function in individuals who had used ubrogepant to treat a migraine episode within the preceding 14 days.

Background

Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine in adults. Few studies have evaluated the real‐world effectiveness of ubrogepant.

Methods

The UNIVERSE study was an observational, cross‐sectional survey conducted between February 2021 and April 2021 in US adult Migraine Buddy application (app) users currently treated with ubrogepant. Individuals who were 18 years of age or older and reported at least one dose of ubrogepant in the previous 14 days completed a 30‐question survey in the app. The survey assessed respondent demographics, migraine history, acute treatment patterns, and treatment satisfaction with ubrogepant. Respondents also reported prior acute medication use and reasons for switching to ubrogepant.

Results

Of the 1303 ubrogepant users contacted, 302 (23.2%; 50 mg, 120 participants; 100 mg, 182 participants) were included in this study. The mean (standard deviation) age was 41.9 (11.2) years, and 90.1% (272/302) were female. Satisfaction with migraine relief at 2, 4, and 24 h post‐dose was reported by 75.8% (229/302), 83.4% (252/302), and 78.5% (237/302) of participants, respectively. Satisfaction with the ability to think clearly after taking ubrogepant was reported by 85.1% (257/302) of participants, and 83.8% (253/302) were satisfied with their ability to return to normal function. Furthermore, 90.7% (274/302) of participants reported that they were likely to continue using ubrogepant to treat their migraine. Most participants (n = 264 [87%]) reported switching to ubrogepant due to inadequate treatment response with their previous treatment. In this subgroup, comparable outcomes were observed with respect to satisfaction with migraine relief, ability to think clearly, and return to normal function.

Conclusions

Ubrogepant demonstrated real‐world effectiveness in the acute treatment of migraine, as evidenced by high levels of treatment satisfaction and a strong indication of their intent to continue using the medication.
‘Leaving the Door Open’: Perspectives on Decision‐Making for Non‐Emergency Diabetes‐Related Amputation
Authors: Ong Emilee Kim Ming , Murray Carolyn , Hillier Susan , Causby Ryan
Published: September 2024

Introduction

Having a lower extremity amputation is a life‐changing decision for people living with a diabetes‐related foot ulcer. Although previous research has described both positive and negative lifestyle and function outcomes of diabetes‐related amputations, limited research has been conducted on the decision‐making processes leading up to the amputation. This study aimed to explore the perspectives of persons, healthcare practitioners and experts (including academics and specialists) on decision‐making for people with a diabetes‐related foot ulcer who may require a non‐emergency amputation.

Methods

A qualitative descriptive study using semi‐structured interviews enabled people to share their thought processes when making decisions for amputation. Twenty‐six participants were interviewed, including nine people with a diabetes‐related foot ulcer or amputation, nine health practitioners and eight experts located across five countries. There were 13 female and 13 male participants. Thematic analysis was used for data analysis.

Results

Four themes described the decision‐making considerations for amputation: ‘Balancing the evidence in decision‐making’, ‘Trust, respect and timing of conversations inform decision‐making’, ‘Tailoring decisions for individual circumstance’ and ‘Reaching the tipping point in decisions for the future’. Work commitments, functional and lifestyle impacts of amputation, the presence of support networks and clinical wound features formed the evidence for a decision for amputation.

Conclusion

Understanding quality of life needs ensured that decisions for amputation addressed expectations and lifestyle needs. Living with a diabetes‐related foot ulcer presented daily challenges that pushed people to a tipping point, at which amputation was considered to overcome these hardships and enable them to move on to the next chapter of their life. Further research is required to understand how person‐centred factors can be better incorporated alongside objective clinical assessments in decisions for amputation.

Patient or Public Contribution

People with diabetes‐related foot ulcers, health practitioners and experts shared their perspectives on the decision‐making process for amputation through one‐to‐one interviews. Consideration of the person in the context of their life, environment and personal needs alongside the pathological factors is warranted.
The safety of same‐day discharge following percutaneous coronary intervention in regional Australia
Authors: Chia Justin , Wilson Angus , Law David , Kelly Maura , Lambert Benjamin
Published: September 2024

Background

Same‐day discharge (SDD) following percutaneous coronary intervention (PCI) has proven safe, and global adoption of this strategy has been increasing rapidly. These data are predominantly derived from high‐volume, metropolitan centres with a relative paucity of data from regional and remote settings.

Aims

The primary objective of this study was to evaluate the outcomes of a same‐day, criteria‐led discharge strategy following elective transradial PCI in a regional setting.

Methods

This is a retrospective, single‐centre cohort study. Consecutive outpatients aged ≥18 years presenting for elective transradial invasive coronary angiography between March 2019 and February 2024 were included in the analysis. We report the primary composite outcome of 30‐day all‐cause mortality and unplanned hospital readmission and compare proportions between those who were discharged on the day of their procedure with those admitted overnight in hospital and discharged the next day.

Results

A total of 555 eligible patients were identified, of which 330 (60%) were discharged on the day of their procedure. The composite primary end‐point occurred in seven (2%) of the SDD patients and in six (3%) of the overnight admission patients (relative risk = 0.80; 95% confidence interval = 0.27–2.34; P = 0.68). No significant differences were seen in rates of readmission, or in other clinical outcomes assessed, including death, myocardial infarction, stroke and vascular complications or bleeding.

Conclusion

In a regional setting, SDD following elective transradial PCI, in select patients, is a safe approach which was not associated with higher rates of unplanned readmission or adverse clinical outcomes.
Optical and Mechanical Properties of the Multi‐Transition Zones of a Translucent Zirconia
Authors: Vardhaman Sonaj , Borba Marcia , Kaizer Marina R. , Kim Do Kyung , Zhang Yu
Published: September 2024

Objective

To characterize the composition, flexure resistance, and optical properties of a multilayer translucent zirconia in relation to its multi‐transition zones.

Materials and Methods

A multilayer zirconia (5Y/4Y) and a conventional 3 mol% yttria partially stabilized zirconia (3Y) were investigated. Bar‐shaped specimens were obtained from the enamel and dentin layers, and the vertical cross‐section of 5Y/4Y (N = 10). A four‐point flexural (σf) test was performed using a universal testing machine (1.0 mm/min). Plate‐shaped specimens (N = 6) were also produced from the enamel, transition 1, transition 2, and dentin layers. Translucency parameters (TPab and TP00) were determined using a dental spectrophotometer (N = 6). X‐ray fluorescence and X‐ray diffraction techniques were used to analyze elemental (N = 2) and phase compositions (N = 2), respectively. Data were analyzed using analysis of variance (ANOVA) and Tukey's test (α = 0.05).

Results

The yttrium content and σf varied between layers of 5Y/4Y. 3Y had the highest σf, followed by dentin. Enamel and cross‐section showed lower and statically similar σf. 3Y and dentin groups had similar but statistically lower TPab and TP00 than the enamel.

Conclusions

Different layers of multilayered zirconia have distinct compositions, which affect their mechanical and optical properties. The weak enamel layer compromises the mechanical properties of cross‐sectional specimens.

Clinical Significance

The development of novel cubic‐containing multilayer zirconia ceramics to produce monolithic restorations brings new challenges to dental clinicians and laboratory technicians. The CAD/CAM design of multilayered 5Y/4Y restorations should consider the esthetic and mechanical requirements of each clinical case, as different properties are found in the different layers of these materials.
Sex differences in quantitative ultrasonographic measurements of the rectus femoris in children
Authors: Cruz‐Montecinos Carlos , Pinto Matheus D. , Pinto Ronei S.
Published: September 2024

The distribution and amount of intramuscular fat and fibrous tissue can be influenced by biological sex and impact muscle quality in both the functional (force‐generating capacity) and morphological (muscle composition) domains. While ultrasonography (US) has proven effective in assessing age‐ or sex‐related differences in muscle quality, limited information is available on sex differences in children. Quantitative ultrasonographic measurements, such as echo intensity (EI), EI bands (number of pixels across 50‐unit intervals) and texture, may offer a comprehensive framework for identifying sex differences in muscle composition. The aim of our study was to examine the effect of sex on the rectus femoris (RF) muscle quality in children. We used EI (mean and bands) and texture as muscle quality estimates derived from B‐mode US. We hypothesised that RF muscle quality differs significantly between girls and boys. Additionally, we also hypothesised that there is a significant correlation between EI bands and texture. Forty‐four non‐active healthy children were recruited (n = 22 girls, 12.8 ± 1.5 years; and n = 22 boys, 13.5 ± 1.2 years). RF was assessed using EI mean, EI bands, and texture analysis (homogeneity and correlation) using the Gray‐Level Co‐Occurrence Matrix. The results revealed significant (p < 0.05) sex differences in RF EI bands and texture. Boys displayed higher values in the 0–50 EI band and had more homogeneous muscle texture than girls. Conversely, girls displayed greater values in the 51–100 EI band and had less homogenous texture compared to boys (p < 0.05). A positive correlation was observed between the 0–50 EI band and muscle homogeneity. However, the 51–100 EI band correlated negatively with homogeneity (p < 0.05), particularly for girls. In conclusion, our study revealed sex‐specific differences in mean EI, EI bands, and texture of the RF muscle in children. The variations in the correlations between the first and second EI bands and texture reveal different levels of homogeneity in each band. This indicates that distinct muscle tissue constituents, such as intramuscular fat and/or connective tissue, may be reflected in EI bands. Overall, the methods used in this study may be useful for examining muscle quality in healthy children and those with medical conditions.