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Abstract Habitual consumption of low-calorie sweeteners (LCS) during juvenile-adolescence can lead to greater sugar intake later in life. Here, we investigated if exposure to the LCS Acesulfame Potassium (Ace-K) during this critical period of development reprograms the taste system in a way that would alter hedonic responding for common dietary compounds. Results revealed that early-life LCS intake not only enhanced the avidity for a caloric sugar (fructose) when rats were in a state of caloric need, it increased acceptance of a bitterant (quinine) in Ace-K-exposed rats tested when middle-aged. These behavior shifts, which endured months after the end of Ace-K exposure, were accompanied by widespread changes in the peripheral taste system. The anterior tongue had fewer fungiform taste papillae, and the circumvallate papillae had a reduced anterior to posterior span and diminished expression of genes involved in sweet reception, sweet and bitter intracellular signaling, fructose transport, and cellular progeneration in the Ace-K-exposed rats. Ace-K exposure also led to a significant reduction in dopamine-producing cells of the ventral tegmental area. The collective findings reveal that LCS intake early in life alters the taste-brain axis and the behavioral responsiveness to both positive and negative tastants that are important determinants of dietary preferences.

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques. One such advanced technique is the Restriction Spectrum Imaging restriction score (RSIrs), an imaging biomarker that has been shown to improve quantitative accuracy of patient-level csPCa detection. Advanced Restriction imaging and reconstruction Technology for Prostate MRI (ART-Pro) is a multisite, multinational trial that aims to evaluate whether IV contrast can be avoided in the setting of standardized, state-of-the-art image acquisition, with or without addition of RSIrs. Additionally, RSIrs will be evaluated as a stand-alone, quantitative, objective biomarker. ART-Pro will be conducted in two stages and will include a total of 500 patients referred for multiparametric prostate MRI with a clinical suspicion of prostate cancer at the participating sites. ART-Pro-1 will evaluate bpMRI, mpMRI, and RSIrs on the accuracy of expert radiologists’ detection of csPCa and will evaluate RSIrs as a stand-alone, quantitative, objective biomarker. ART-Pro-2 will evaluate the same MRI techniques on the accuracy of nonexpert radiologists’ detection of csPCa, and findings will be evaluated against the expertly created dataset from ART-Pro-1. The primary endpoint is to evaluate whether bpMRI is noninferior to mpMRI among expert (ART-Pro-1) and nonexpert (ART-Pro-2) radiologists for the detection of grade group ≥2 csPCa. This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT06579417) at ClinicalTrials.gov. Patient accrual at the first site (UC San Diego) began in December 2023. Initial results are anticipated by the end of 2026.

Abstract Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children. In this study, we developed an in silico model describing the pulmonary immune response to a common allergen, house dust mite, to investigate its downstream impact on the pathophysiology of asthma, including airway eosinophilic inflammation, remodelling, and lung function. We hypothesised that altered epithelial function following allergen exposure determines the onset of airway remodelling and abnormal lung function, which are irreversible with current asthma therapies. We calibrated the in silico model using age appropriate in vivo data from neonatal and adult mice. We validated the in silico model using in vivo data from mice on the effects of current treatment strategies. The in silico model recapitulates experimental observations and provides an interpretable in silico tool to assess airway pathology and the underlying immune responses upon allergen exposure. The in silico model simulations predict the extent of bronchial epithelial barrier damage observed when allergen sensitisation occurs and demonstrate that epithelial barrier damage and impaired immune maturation are critical determinants of reduced lung function and asthma development. The in silico model demonstrates that both epithelial barrier repair and immune maturation are potential targets for therapeutic intervention to achieve successful asthma prevention.

Family scholarship has documented negative associations between ambivalence and well-being in the context of parent-adult child relationships. As sibling ties remain salient throughout later life, ambivalence experienced in sibling relationships might also be related to older adult well-being. The purpose of this study was to examine the associations between sibling ambivalence and both psychological and physical well-being of older adults, as well as differences in these links by sibling gender composition. Data came from 702 older adults (392 women) who were 64.58 years old on average (SD = 4.51). Structural equation modeling using FIML revealed that participants who felt more ambivalence toward their siblings reported poorer psychological well-being. However, a multiple group analysis showed that this association was only significant for brother-brother pairs. Findings suggest the need to further investigate the implication of sibling ambivalence for psychological well-being in later life, especially for brothers. [ABSTRACT FROM AUTHOR]

One of the most surprising and important findings of the first human landings on the Moon was the discovery of a very fine layer of lunar dust covering the entire surface of Moon along with the negative impacts of this dust on the well-being and operational effectiveness of the astronauts, their equipment, and instrumentation. The United States is now planning for human missions to Mars, a planet where dust can also be expected to be ubiquitous for many or most landing sites. For these missions, the design and operations of key hardware systems must take this dust into account, especially when related to crew health and safety. Improved understanding of Martian dust characteristics can inform its potential to also perform transport of microorganisms, both those inadvertently brought to Mars by the astronauts, or, if Martian microorganisms exist, the potential for their inadvertent return to Earth with the astronauts. Careful planning and design are needed to assure that future missions do not violate the United Nations Outer Space Treaty (1967) signed by all spacefaring nations. In this paper, we review the impact of lunar dust on the Apollo missions and identify several questions about dust in the atmosphere of Mars that may be answered by the curated samples that would be returned by the planned Mars Sample Return (MSR) Campaign. These answers would not only provide an opportunity to better understand the history of Mars but could also reduce uncertainty in charting the future of humanity's exploration of the planet. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the utility of ultrasound (US) imaging for diagnosis of abnormal tracheal morphology, such as tracheal cartilaginous sleeves (TCS), in patients with syndromic craniosynostosis (SC). Study Design: Age‐matched cohort study. Setting: Tertiary pediatric hospital. Methods: Two age‐matched cohorts were identified: patients with SC and known TCS based upon airway endoscopy and normal controls without tracheal pathology. Enrolled patients underwent awake US of the neck which were randomized and reviewed by blinded pediatric radiologists and rated on presence or absence of normal tracheal cartilage morphology and visualization or nonvisualization of a tracheostomy tube. Fisher's exact test was used to assess pooled data. Fleiss' Kappa (κ) was calculated to assess inter‐rater reliability. Results: Ten patients were included in each cohort. Control patients were gender and age‐matched to TCS patients with a mean difference of 3.7 months (±3.9 months). Across all raters, cartilage type was correctly identified in 93% (95% confidence interval [CI]: 84%‐98%) and tracheostomy visualization in 97% (95% CI: 89%‐99%). The sensitivity and specificity for detection of abnormal cartilage pathology was 87% and 100%, respectively. Inter‐rater reliability for cartilage assessment was κ = 0.88 (95% CI: 0.67‐1.00, P <.05) and 0.83 (95% CI: 0.58‐1.00, P <.05) for tracheostomy presence. Conclusion: This study demonstrated that tracheal US is a feasible, accurate screening tool for TCS, and can be successfully performed non‐sedated in patients up to 18 years of age, both with and without tracheostomy tubes in place. [ABSTRACT FROM AUTHOR]

Asthma affects approximately 300 million individuals worldwide and the onset predominantly arises in childhood. Children are exposed to multiple environmental irritants, such as viruses and allergens, that are common triggers for asthma onset, whilst their immune systems are developing in early life. Understanding the impact of allergen exposures on the developing immune system and resulting alterations in lung function in early life will help prevent the onset and progression of allergic asthma in children. In this study, we developed an in silico model describing the pulmonary immune response to a common allergen, house dust mite, to investigate its downstream impact on the pathophysiology of asthma, including airway eosinophilic inflammation, remodelling, and lung function. We hypothesised that altered epithelial function following allergen exposure determines the onset of airway remodelling and abnormal lung function, which are irreversible with current asthma therapies. We calibrated the in silico model using age appropriate in vivo data from neonatal and adult mice. We validated the in silico model using in vivo data from mice on the effects of current treatment strategies. The in silico model recapitulates experimental observations and provides an interpretable in silico tool to assess airway pathology and the underlying immune responses upon allergen exposure. The in silico model simulations predict the extent of bronchial epithelial barrier damage observed when allergen sensitisation occurs and demonstrate that epithelial barrier damage and impaired immune maturation are critical determinants of reduced lung function and asthma development. The in silico model demonstrates that both epithelial barrier repair and immune maturation are potential targets for therapeutic intervention to achieve successful asthma prevention. [ABSTRACT FROM AUTHOR]

Objectives To develop a reproducible, reliable clinical index of alveolar bone grafting (ABG) outcome based on the eruption position of the cleft canine tooth and determine the association between eruption position and radiographic outcome at 6 months post-grafting. Methods Children with complete, non-syndromic, unilateral/bilateral cleft lip and palate in the West of Scotland were identified. Post-ABG radiographic outcome (Kindelan index) and canine eruption position in children with a cleft of the alveolus who had undergone ABG were documented. A Kindelan score was assigned to the 6-month post-bone-graft radiograph. Following canine tooth eruption, four-point clinical index scale (CIS) scores were assigned to maxillary occlusal images taken prior to commencement of definitive orthodontics; 1—canine eruption in alveolar crest, 2—canine eruption buccal to alveolar crest, 3—canine eruption palatal to alveolar crest, and 4—canine impaction. Intra and inter-rater reliability was assessed using Cohen and Fleiss kappa's, respectively. Duration of orthodontics treatment, number of orthodontic clinic visits, and clinical management of the cleft site space were noted. Results Eighty-three patients representing 98 bone graft sites were identified. CIS scoring intra- and inter-rater reliability was 0.69–0.99 and 0.63–0.75, respectively. CIS score was associated with reduced visits (P  = .015), months in orthodontics (P  = .009), and likelihood of space closure (P  = .006). Limitations This is a retrospective study with small numbers but is comparative to other similar studies in the literature. Conclusions The CIS presented appears to be a reliable index of ABG outcome. It also demonstrates an association with the burden of orthodontic care post-cleft alveolar bone graft. [ABSTRACT FROM AUTHOR]

The editorial discusses the importance of evaluating systematic reviews and meta-analyses in orthopedic research. It highlights the need for discernment in including source studies in these analyses to avoid unreliable findings. The editorial emphasizes the significance of follow-up duration in assessing the validity of research outcomes and suggests minimum standards for different types of studies. Authors are encouraged to justify surveillance periods and address methodological shortcomings in their papers. The editorial underscores the importance of considering various biases and quality assessments when evaluating research in orthopedics. [Extracted from the article]

OBJECTIVE To evaluate the sedation quality of an IM injection of a commercially available medetomidine-vatinoxan combination (ZEN) in healthy goats and sheep and discern species differences in cardiopulmonary parameters. METHODS 10 apparently healthy adult university-owned research Black Bengal–crossbreed goats and 10 adult Gulf Coast native and Katahdin sheep were enrolled in this prospective experimental study from June 27 to July 27, 2023. All animals were sedated on 1 occasion with 0.06 mL of ZEN/kg, IM (0.03 mg of medetomidine/kg and 0.6 mg of vatinoxan hydrochloride/kg). Cardiopulmonary variables including heart rate, arterial blood pressure, and arterial blood gas parameters were recorded along with sedation depth and duration. Any animals still sedated after 150 minutes received 0.01 mg of atipamezole/kg. RESULTS The mean ± SD of the total sedation time for sheep and goats was 102.80 ± 10.90 minutes and 133.50 ± 32.63 minutes, respectively. Profound reliable sedation was achieved in all but 1 animal. Hypoxemia was observed in sheep and goats (11 of 20 animals total). Hypotension was seen in 3 of 10 goats. CONCLUSIONS In sheep and goats, ZEN at 0.06 mL/kg, IM, caused profound sedation. Total sedation time was significantly longer in goats than in sheep. CLINICAL RELEVANCE In the presence of oxygen supplementation, ZEN at 0.06 mL/kg, IM, may be an acceptable sedation choice for apparently healthy Gulf Coast native and Katahdin sheep, but not goats; however, preexisting hypokalemia or pulmonary disease are contraindications for the use of ZEN in sheep. [ABSTRACT FROM AUTHOR]

Chronic lung diseases including asthma are characterized by an abnormal immune response and active tissue remodeling. These changes in the architecture of the tissue are a fundamental part of the pathology across the life course of patients suffering from asthma. Current treatments aim at dampening the immune system hyperactivation, but effective drugs targeting stromal or acellular structures are still lacking. This is mainly due to the lack of a detailed understanding of the composition of the large airways and the cellular interactions taking place in this niche. We and others have revealed multiple aspects of the spatial architecture of the airway wall in response to airborne insults. In this review, we discuss four elements that we believe should be the focus of future asthma research across the life course, to increase understanding and improve therapies: (i) specialized lung niches, (ii) the 3D architecture of the epithelium, (iii) the extracellular matrix, and (iv) the vasculature. These components comprise the main stromal structures at the airway wall, each playing a key role in the development of asthma and directing the immune response. We summarize promising future directions that will enhance lung research, ultimately benefiting patients with asthma., (© 2025 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to assess the efficacy and complication rates of interarytenoid injection augmentation (IAIA) for the treatment of dysphagia in patients 1 year of age and under and to determine if concurrent feeding therapy (FT) affects outcome., Study Design: Retrospective case series., Setting: Tertiary pediatric hospital., Methods: Retrospective review of patients 13 months of age and younger with dysphagia treated by IAIA over a 4-year period. The efficacy of IAIA was determined by comparing perioperative videofluoroscopic swallow studies (VFSS) and Dysphagia Outcome and Severity Scale (DOSS) scores. Complication rates and utilization of concomitant FT were determined by evaluating postoperative admission and follow-up records., Results: Sixty-five patients met inclusion criteria (median age 8 months, interquartile range [IQR]: 7-11). Sixty-seven percent of patients improved on postoperative VFSS scores (median improvement in aspiration of 2 thickness levels, IQR 0-3, P < .0001), and 56% improved in DOSS scores (median increase of 1, IQR: 0-1.5, P < .0001). Ninety-two percent of patients were discharged home on the day of surgery. The 30-day relevant readmission rate was 5%. No patients had intraoperative complications or severe complications at follow-up. No statistical difference in aspiration or DOSS was noted in the concomitant FT cohort due to a lack of sample size., Conclusion: This study demonstrates that IAIA in children under 13 months old shows comparable rates of success and complications to older patients reported in the literature. No patients had long-term complications and most were discharged home on the day of surgery. More studies are needed to determine the effect of concomitant FT on IAIA., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Social cognition may play a central role in many schizotypal personality characteristics, such as suspiciousness, constricted affect, social anxiety, and lack of close relationships. This study investigated how factors relevant to self-other distinction (i.e., emotion contagion and personal distress) were related to social schizotypal personality traits, in two experiments involving healthy young adults. Subclinical depressive symptoms, alexithymia, and obsessive-compulsive traits, were explored as potential mediators of the relationship between personal distress and schizotypy. Experiment 1 showed that high sadness contagion predicted personal distress, which in turn predicted cognitive disorganization. This relationship was mediated by low mood. Experiment 2 revealed that high personal distress predicted excessive social anxiety and ideas of reference, as well as obsessive-compulsive tendencies. Personal distress also predicted difficulty identifying feelings, an aspect of alexithymia that could develop as a result of difficulties in disentangling emotional experiences related to the self and others. However, it was difficulty describing feelings that predicted social anhedonia, constricted affect, and no close friends. While personal distress was a positive predictor of empathic concern, social anhedonia was a negative predictor. These findings suggest that personal distress and difficulty identifying feelings predict more anxious and disorganized aspects of schizotypy, as well as subclinical depressive and obsessive-compulsive symptoms. Future research should investigate whether this profile, which may be more closely related to low self-other distinction, contrasts with a more socially avoidant presentation, characterized by negative schizotypal traits such as social anhedonia and lower empathy. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Bovine uterine prolapse is a common but emergent condition typically arising in the time surrounding calving. Without treatment, it can result in tissue trauma, infection, hemorrhage, and death. Teaching veterinary students to perform uterine prolapse reduction has historically been dependent upon adequate clinical caseload requiring the procedure. This study sought to develop and collect validation evidence for a silicone bovine uterine prolapse reduction model and associated scoring rubric to enable procedural practice without the presentation of live animals requiring the procedure. This study utilized a validation framework consisting of content evidence (expert opinion), internal structure evidence (reliability of scores produced by the rubric), and relationship with other variables evidence (level of training, novice-to-expert comparison). Veterinary students ( n = 37, novices) and veterinarians ( n = 11, experts) performed the procedure on the model while being video recorded. All participants then completed a survey about the model. Veterinarians' survey results indicated that the model adequately represented the task and was suitable for teaching and assessing veterinary students' skill in the procedure (content evidence). Scores produced by the rubric had a marginal Cronbach's alpha (.607), suggesting that the rubric may be adequate for low-stakes assessment but would require additional items or modification in order to improve reliability and be suitable for high-stakes assessment (internal structure evidence). Finally, experts achieved higher total rubric scores than novices did (relationship with other variables evidence). This study demonstrated content evidence and relationship with other variables evidence for the bovine uterine prolapse model, indicating its usefulness for teaching this important clinical skill.

As Artificial Intelligence (AI) technologies become more integrated into clinical settings to optimize care, healthcare professionals (HCPs) will need to become more adept in responsibly using these novel technologies to augment patient care. A qualitative study, consisting of semi-structured interviews was conducted to explore the informational needs of HCPs and gaps in current AI education. Participants, consisting of educators and learners, were recruited from AI programs. The interview data were analyzed using inductive thematic analysis. Three themes were identified, addressing the need for (1) developing a longitudinal AI curriculum to transform the mindset, skillset, and toolset of providers, (2) cultivating an active learning approach to foster knowledge mobilization and optimize the use of AI tools in the provision of care, and (3) fostering a multidisciplinary approach to AI curriculum design is essential to promote collaborative efforts among HCPs in implementing AI tools. This study identified five key recommendations to prepare HCPs with the knowledge and skills necessary for an AI-driven future.

Rhesus macaques (Macaca mulatta) have long been used as a model for the evolution of some aspects of human social behavior and they are among the most completely understood species of the macaque genus. Rhesus macaques have a despotic dominance hierarchy with a well-documented facial display repertoire. However, we know little about the ontogenetic changes in gross facial musculature and how this might relate to corresponding facial display behavior. In an effort to illuminate our understanding, we dissected facial masks from 13 M. mulatta cadavers that died naturally, shortly after birth or were stillborn, and we compared these results to those from adult rhesus macaques. Results reveal that, unlike the adults in the present study, infant rhesus macaques have extrinsic external ear muscles and muscles associated with the lower lip that are very gracile and poorly developed. Musculature associated with the upper lip and nares are well developed, individually distinct, and robust, like those of the adults in our sample and adult M. mulatta. However, we were unable to locate the zygomaticus major muscle in any fetal/infant sample. These results may reflect simple variation in mimetic muscle ontogeny, differences related to facial allometry, or they could reflect a behaviorally meaningful adaptation to different life stages of macaque ontogeny., (© 2025 Wiley Periodicals LLC.)

Cells under high confinement form highly polarized hydrostatic pressure-driven, stable leader blebs that enable efficient migration in low adhesion, environments. Here we investigated the basis of the polarized bleb morphology of metastatic melanoma cells migrating in non-adhesive confinement. Using high-resolution time-lapse imaging and specific molecular perturbations, we found that EGF signaling via PI3K stabilizes and maintains a polarized leader bleb. Protein activity biosensors revealed a unique EGFR/PI3K activity gradient decreasing from rear-to-front, promoting PIP3 and Rac1-GTP accumulation at the bleb rear, with its antagonists PIP2 and RhoA-GTP concentrated at the bleb tip, opposite to the front-to-rear organization of these signaling modules in integrin-mediated mesenchymal migration. Optogenetic experiments showed that disrupting this gradient caused bleb retraction, underscoring the role of this signaling gradient in bleb stability. Mathematical modeling and experiments identified a mechanism where, as the bleb initiates, CD44 and ERM proteins restrict EGFR mobility in a membrane-apposed cortical actin meshwork in the bleb rear, establishing a rear-to-front EGFR-PI3K-Rac activity gradient. Thus, our study reveals the biophysical and molecular underpinnings of cell polarity in bleb-based migration of metastatic cells in non-adhesive confinement, and underscores how alternative spatial arrangements of migration signaling modules can mediate different migration modes according to the local microenvironment.