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Understanding the interplay between biology and mechanics in tissue architecture is challenging, particularly in terms of 3D tissue organization. Addressing this challenge requires a biological model enabling observations at multiple levels from cell to tissue, as well as theoretical and computational approaches enabling the generation of a synthetic model that is relevant to the biological model and allowing for investigation of the mechanical stresses experienced by the tissue. Using a monolayer human colon epithelium organoid as a biological model, freely available tools (Fiji, Cellpose, Napari, Morphonet, or Tyssue library), and the commercially available Abaqus FEM solver, we combined vertex and FEM approaches to generate a comprehensive viscoelastic finite element model of the human colon organoid and demonstrated its flexibility. We imaged human colon organoid development for 120 hours, following the evolution of the organoids from an immature to a mature morphology. According to the extracted architectural/geometric parameters of human colon organoids at various stages of tissue architecture establishment, we generated organoid active vertex models. However, this approach did not consider the mechanical aspects involved in the organoids' morphological evolution. Therefore, we applied a finite element method considering mechanical loads mimicking osmotic pressure, external solicitation, or active contraction in the vertex model by using the Abaqus FEM solver. Integration of finite element analysis (FEA) into the vertex model achieved a better fit with the biological model. Therefore, the FEM model provides a basis for depicting cell shape, tissue deformation, and cellular-level strain due to imposed stresses. In conclusion, we demonstrated that a combination of vertex and FEM approaches, combining geometrical and mechanical parameters, improves modeling of alterations in organoid morphology over time and enables better assessment of the mechanical cues involved in establishing the architecture of the human colon epithelium., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Laussu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Activated intramolecular singlet fission is known to occur in the conjugated polymer polythienylene-vinylene (P3TV). Instead, efficient intersystem crossing has been observed in a short 3-alkyl(thienylene-vinylene) dimer. Here, we investigate a series of oligomers covering the conjugation length gap between the dimer and polymer. We confirm that the polymer and longer oligomers undergo activated intramolecular singlet fission, while the shorter oligomers with less than 3 units predominantly undergo efficient intersystem crossing. For the longer oligomers, the intermediate state of singlet fission is assigned to the 3A g - covalent state of triplet pair character, as predicted by several computational studies. Our results point to potential pitfalls when assigning triplet production pathways solely with transient absorption spectroscopy.

Subjective weighting methods are widely employed to determine criteria weights in multi-criteria decision-making (MCDM) environment. Inputs from decision-makers, including opinions, assessments, assumptions, evaluations, interpretations, expectations, and judgments, are primarily relied upon in these methods. Significant challenges are faced due to two primary factors: the inherent uncertainty in inputs and the process of pairwise comparisons. These challenges increase the uncertainty regarding the derived weights, raising concerns about the reliability of such approaches. This paper introduces a novel MCDM method called Soft Clusters-Rectangles (SCR) to overcome such limitations. This method distinguishes itself by avoiding pairwise comparisons and adopting a fuzzy approach to address uncertainty. Weights are calculated based on criteria membership values across three defined clusters, namely immaterial, mediocre, and vital. Each cluster represents a distinct range of importance. Analytic geometry is also used by computing the areas of multiple rectangles to determine the final weights. The application of SCR method is demonstrated through a case study on autonomous vehicle route selection problem. The results are thoroughly examined through comprehensive analysis. The findings reveal that this method not only avoids the challenges posed by pairwise comparison-based methodologies but also exhibits similarities with objective weighting techniques, often yielding results more comparable to those produced by hybrid methods., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Dental anomalies are frequent in boars and pigs, and they generally affect the first premolar loci. The prevalence of these dental anomalies was investigated in a large number of populations around the world. These studies mainly focused on the influence of domestication, size, sexual dimorphism or food hardness on these anomalies. However, they rarely considered ontogenetic aspects, while these are crucial for understanding their aetiology during animal growth and how the dental row-jaw complex is affected. Here, we studied the incidence of missing first upper and lower premolars in a French population of captive wild boars to discuss the functional and developmental reasons for missing teeth and to assess the impact of missing teeth on the growth of the dental row-jaw complex. Using the CT-scan data of the cranium and mandible of 24 wild boars investigated six times each during their growth, and presenting a balanced sex ratio, we recorded the number of missing teeth. We then quantified the shape of the upper and lower jaws using 3D geometric morphometrics. We found a similar prevalence of missing first premolar (37.5%) between the upper and the lower jaws, which is higher than the frequencies observed in most continental populations of wild boars. The increasing number of anomalies during ontogeny suggests a relaxed constraint on the dentition associated with a different feeding behaviour in captivity. The absence of first premolars does not appear to be associated with size variation or sexual dimorphism, nor does it affect the place of the dentition within the jaw, the latter being more influenced by the dimorphic shape of the canines and the timing of dental eruption., (© 2025 Wiley Periodicals LLC.)

Patients with familial adenomatous polyposis (FAP) harbor mutations in the APC gene and will develop adenoma and early colorectal cancer. There is no validated treatment, and animal models are not sufficient to study FAP. Our aim was to investigate the early events associated with FAP using the intestinal organoid model in a single-center study using biopsies from nonadenomatous and adenomatous colonic mucosa of FAP patients and from healthy controls (HCs). We analyzed intestinal stem cell (ISC) activity and regulation through organoid development and expression of mRNA and proteins, as well as within colonic crypts. We used several compounds to regulate the signaling pathways controlling ISCs, such as WNT, EGFR, PI3K-AKT, TGF-β, yes-associated protein (YAP), and protease-activated receptors. In addition to their high proliferative capacity, nonadenomatous and adenomatous organoids were characterized by cysts and cysts with buds, respectively, suggesting abnormal maturation. Adenomatous organoids were enriched in the stem cell marker LGR5 and dependent on EGF and TGF-β for their growth. Downstream of EGFR, AKT, β-catenin, and YAP were found to be activated in the adenomatous organoids. While the p110β isoform of PI3K was predominant in adenomatous organoids and essential for their growth, p110α was associated with the immature state of nonadenomatous organoids. We conclude that organoids offer a relevant model for studying FAP, and this work highlights abnormal behaviors of immature cells in both nonadenomatous and adenomatous mucosa of FAP patients, which could be targeted therapeutically. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: Pressure on carotid artery by hyoid bone may influence plaque formation. We studied CTA-based hyoid-carotid anatomical interaction and its relationship with carotid stenosis degree and stenosis-related stroke., Methods: We retrospectively analysed pre-operative CTA of 205 consecutive adults having undergone carotid endarterectomy (CEA) for asymptomatic or symptomatic stenosis. Radiological measurements were: degree stenosis, hyoid-carotid distance, carotid position in regard to hyoid, and hyoid morphology., Results: In total, 410 carotids (including 114 symptomatic and 296 asymptomatic stenotic and non-stenotic carotids) from 205 CEA patients (median age 74, 72% men) were analysed. Median carotid stenosis was 61% (70% for symptomatic and 51% for asymptomatic carotids, p<0.0001; 70% for CEA and 30.5% for non-CEA carotids, p<0.0001). None of the other radiological parameters differed between asymptomatic/symptomatic carotids, between non-CEA/CEA carotids, or between asymptomatic/symptomatic patients. Median hyoid-carotid distance was 4.3mm, with 82% of carotids in posterolateral quadrant position in regard to the hyoid. There was no correlation between stenosis degree and hyoid-carotid distance (rho=-0.039), hyoid width (rho=-0.079), length (rho=0.007) or circumferential length (rho=-0.005), and stenosis degree was comparable between different carotid position quadrants (p=0.51)., Conclusions: Hyoid-carotid distance, hyoid position and morphology are not correlated with the degree of carotid stenosis or symptomatic carotid stenosis., Clinical Trial Registration-Url: http://www., Clinicaltrials: gov: Unique identifier: NCT05349526., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The success of gene therapy hinges on the effective encapsulation, protection, and compression of genes. These processes deliver therapeutic genes into designated cells for genetic repair, cellular behavior modification, or therapeutic effect induction. However, quantifying the encapsulation efficiency of small molecules of interest like DNA or RNA into delivery carriers remains challenging. This work shows how super-resolution microscopy, specifically direct stochastic optical reconstruction microscopy (dSTORM), can be employed to visualize and measure the quantity of DNA entering a single carrier. Utilizing pNIPAM/bPEI microgels as model nano-carriers to form polyplexes, DNA entry into the carrier is revealed across different charge ratios at temperatures below and above the volume phase transition of the microgel core. The encapsulation efficiency also depends on DNA length and shape. This work demonstrates the uptake of the carrier entity by primary derived macro-phages and showcases the cell viability of the polyplexes. The study shows that dSTORM is a potent tool for fine-tuning and creating polyplex microgel carrier systems with precise size, shape, and loading capacity at the individual particle level. This advancement shall contribute significantly to optimizing gene delivery systems., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Importance: International guidelines lack consistency in their recommendations regarding routine imaging in the follow-up after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). Consequently, follow-up strategies differ between centers worldwide., Objective: To compare clinical outcomes, including recurrence-focused treatment and survival, in patients with PDAC recurrence who received symptomatic follow-up or routine imaging after pancreatic resection in international centers affiliated with the European-African Hepato-Pancreato-Biliary Association (E-AHPBA)., Design, Setting, and Participants: This was a prospective, international, cross-sectional study. Patients from a total of 33 E-AHPBA centers from 13 countries were included between 2020 and 2021. According to the predefined study protocol, patients who underwent PDAC resection and were diagnosed with disease recurrence were prospectively included. Patients were stratified according to postoperative follow-up strategy: symptomatic follow-up (ie, without routine imaging) or routine imaging., Exposures: Symptomatic follow-up or routine imaging in patients who underwent PDAC resection., Main Outcomes and Measures: Overall survival (OS) was estimated with Kaplan-Meier curves and compared using the log-rank test. To adjust for potential confounders, multivariable logistic regression was used to evaluate the association between follow-up strategy and recurrence-focused treatment. Multivariable Cox proportional hazard analysis was used to study the independent association between follow-up strategy and OS., Results: Overall, 333 patients (mean [SD] age, 65 [11] years; 184 male [55%]) with PDAC recurrence were included. Median (IQR) follow-up at time of analysis 2 years after inclusion of the last patient was 40 (30-58) months. Of the total cohort, 98 patients (29%) received symptomatic follow-up, and 235 patients (71%) received routine imaging. OS was 23 months (95% CI, 19-29 months) vs 28 months (95% CI, 24-30 months) in the groups who received symptomatic follow-up vs routine imaging, respectively (P = .01). Routine imaging was associated with receiving recurrence-focused treatment (adjusted odds ratio, 2.57; 95% CI, 1.22-5.41; P = .01) and prolonged OS (adjusted hazard ratio, 0.75; 95% CI, 0.56-.99; P = .04)., Conclusion and Relevance: In this international, prospective, cross-sectional study, routine follow-up imaging after pancreatic resection for PDAC was independently associated with receiving recurrence-focused treatment and prolonged OS.

Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used 1 H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice. Nine cohorts of male mice, with six mice per cohort, were used: wild type non-diabetic control mice (WT-NDM), WT-diabetic (WT-DM) mice, Ager knockout non-diabetic (RKO-NDM) and diabetic mice (RKO-DM), Diaph1 knockout non-diabetic (DKO-NDM), and diabetic mice (DKO-DM), WT-NDM mice treated with vehicle, WT-DM mice treated with vehicle, and WT-DM mice treated with RAGE229 (antagonist of RAGE-DIAPH1 interaction). A Point Resolved Spectroscopy (PRESS) sequence for 1 H-MRS, and multi-echo gradient recalled echo (GRE) for CSE were employed. Triglycerides, and free fatty acids in the heart and hind limb obtained from MRS and MRI were compared to those measured using biochemical assays. Two-sided t-test, non-parametric Kruskal-Wallis Test, and one-way ANOVA were employed for statistical analysis. We report that the results were well-correlated with significant differences using MRI and biochemical assays between WT-NDM and WT-DM, as well as within the non-diabetic groups, and within the diabetic groups. Deletion of Ager or Diaph1, or treatment with RAGE229 attenuated diabetes-associated increases in triglycerides in the heart and hind limb in mice. These results suggest that the employment of 1 H-MRS/MRI is a feasible non-invasive modality to monitor metabolic dysfunction in T1D and the metabolic consequences of interventions that block RAGE and DIAPH1., (© 2024 John Wiley & Sons Ltd.)

Pulmonary surfactant is produced by type II alveolar epithelial cells (AEC2) and stored in lamellar bodies (LBs) before secretion. Here, we characterize AEC2 and their LBs in the human lung ultrastructurally and quantitatively. Five human lungs were analyzed by transmission electron microscopy, serial section electron tomography, and stereology. A human lung contained about 24 billion AEC2 with a mean size of about 650 µm 3 . The number of AEC2 as well as the total volume of LBs per lung, about 1.9 mL, strongly correlated with total lung volume. A single AEC2 contained an LB volume of about 74 µm 3 . This amount was packed in about 324 LBs with a mean size of 0.24 µm 3 . Three morphologically distinct subpopulations of LBs were identified: 1 ) isolated LBs which make up the majority (average 300 per AEC2), 2 ) LBs connected to each other via pores (average 23 per AEC2), and 3 ) LBs connected to the plasma membrane via a fusion pore (average 1 per AEC2). Along this sequence of subpopulations, the mean size of LBs increased. LBs that were connected either with each other or to the plasma membrane contained about 14% of an AEC2's LB volume. This is in line with the concept of an intermediate surfactant pool, stored in LBs either directly or indirectly connected to the plasma membrane. In summary, this study provides quantitative reference data on surfactant-storing LBs in AEC2 as well as morphological evidence for an intermediate surfactant pool in the human lung. NEW & NOTEWORTHY Human lung type II alveolar epithelial cells (AEC2) and their surfactant-storing lamellar bodies (LBs) are characterized quantitatively and ultrastructurally by transmission electron microscopy, serial section electron tomography, and stereology. On average, the 24 billion AEC2 in a human lung contain 324 LBs each. An intermediate surfactant pool in the human lung, comprising LBs in AEC2 not only directly but also indirectly connected to the plasma membrane via inter-LB connections, is demonstrated morphologically and characterized quantitatively.

Sepsis is a life-threatening immune response to infection in the body, eventually resulting in fatal organ failure. Current methods utilize blood cultures and quick-Sequential-Organ-Failure-Assessment (qSOFA), but there is a need for more accurate and time-sensitive diagnostic methods to improve survival rates. We present a 3D-printed microfluidic chip that bioconjugates antibodies CD69, CD64, and CD25 to channel surfaces to capture sepsis cells in blood samples and validate it with clinical samples (n = 125 septic, n = 10 healthy). Other variables were taken such as healthy volunteer blood samples and patient demographics to validate and confirm our device's diagnostic ability. Statistical differences were found between healthy volunteer and sepsis patient antigen cell counts (CD69 p-value < 0.001, CD64 p-value < 0.004, CD25 p-value < 0.0009), and were confirmed using principal component analysis. Demographics such as length of stay, age, culture results, and need for surgery also factored into sepsis detection on a smaller scale than the antigen cell counts. The receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.989, 0.988, and 0.992 for CD69, CD64, and CD25, respectively, and a combined biomarker panel of 0.997. Overall, the device performed within a shorter time frame of 4 h compared to standard blood culture tests and was validated for use in detecting sepsis in patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: D Pappas reports financial support was provided by National Institutes of Health. D Pappas reports a relationship with NaMi Diagnostics that includes: non-financial support. D Pappas has patent #10,761,093 licensed to NaMi Diagnostics. Dr. Pappas’s patent on this technology is licensed through NaMi Diagnostics, who have no competing interest in this work. Dr. Pappas has no financial position in NaMi Diagnostics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: We aimed to understand transgender and nonbinary (TNB) young adults' desire to receive gender-affirming medical care (GAMC) before age 18 and identify barriers and facilitators to receiving this care in adolescence. Methods: A cross-sectional survey was administered to TNB young adults presenting for care between ages 18 and 20 in 2023. Descriptive statistics characterized the sample, χ 2 tests with post hoc pairwise comparisons identified differences in desire for gender-affirming medications, outness, and parental consent by gender identity and sex assigned at birth, and t -tests evaluated differences in barriers and facilitators to receiving care by outness to parents. Results: A total of 230 TNB respondents had complete data. Nearly all (94.3%) indicated they desired GAMC before age 18. Half (55.7%) of the respondents reported being out about their gender identity to a parent before age 18. Outness, discussing desire for GAMC, and asking for consent to receive GAMC from a parent were significantly more common among participants who identified as men compared to those who identified as women and among those assigned female at birth compared to those assigned male at birth. No such differences emerged when comparing nonbinary individuals to those who identified as men or women. Lack of parental willingness to consent for GAMC was cited as the primary contributor of not having received care in adolescence. Conclusions: Many TNB young adults desire GAMC in adolescence; however, lack of parental support is a key barrier to receiving this care, suggesting a need for more readily available resources for parents to support TNB adolescents.

Aims: The aim of the study was to develop a comprehensive competency framework for advanced practice nurses in Belgium., Design: A co-design development process was conducted., Methods: This study consisted of two consecutive stages (November 2020-December 2021): (1) developing a competency framework for advanced practice nurses in Belgium by the research team, based on literature and (2) group discussions or interviews with and written feedback from key stakeholders. 11 group discussions and seven individual interviews were conducted with various stakeholder groups with a total of 117 participants., Results: A comprehensive competency framework containing 31 key competencies and 120 enabling competencies was developed based on the Canadian Medical Education Directions for Specialists Competency Framework. These competencies were grouped into seven roles: clinical expert and therapist, organizer of quality care and leader in innovation, professional and clinical leader, collaborator, researcher, communicator and health promoter., Conclusion: The developed competency framework has resemblance to other international frameworks. This framework emphasized the independent role of the advanced practice nurse and provided guidance in a clear task division and delegation to other professionals. It can provide a solid foundation for delivering high-quality, patient-centred care by advanced practice nurses in the years to come., Implications for the Profession: This competency framework can guide further development of advanced practice nursing education in Belgium and represents a starting point for future evaluation of its feasibility and usability in education and clinical practice. Advanced practice nurses and healthcare managers can also use the framework as an instrument for personal and professional development, performance appraisal, and further alignment of these function profiles in clinical practice. Finally, this framework can inform and guide policymakers towards legal recognition of advanced practice nursing in Belgium and inspire the development of advanced practice nursing profiles in countries where these profiles are still emerging., Impact: What problem did the study address? The absence of a detailed competency framework for advanced practice nurses complicates legal recognition, role clarification and implementation in practice in Belgium. A rigorously developed competency framework could clarify which competencies to integrate in future advanced practice nursing education, mentorship programs and practice. What were the main findings? The competency framework outlined seven roles for advanced practice nurses: clinical expert and therapist, organizer of quality care and leader in innovation, professional and clinical leader, collaborator, researcher, communicator, and health promoter. Differentiation from other expert nursing profiles and clinical autonomy of advanced practice nurses were pivotal. Where and on whom will the research have impact? The comprehensive competency framework for advanced practice nurses and the collaborative methodology used can inspire other countries where these profiles are still emerging. The competency framework can be used as an instrument for role clarification, performance appraisals, continuous professional development, and professional (e-)portfolios. The competency framework can guide policymakers when establishing Belgian's legal framework for advanced practice nurses., Reporting Method: The authors have adhered to CONFERD-HP: recommendations for reporting COmpeteNcy FramEwoRk Development in health professions., Patient or Public Contribution: No patient or public contribution in the design of the study. A patient advisory panel commented on the developed competency framework., (© 2024 John Wiley & Sons Ltd.)