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Inducing axial vascularisation of tissue engineering constructs is a well-established method to support tissue growth in large 3-dimensional tissues. Progenitor cell chemotaxis towards axially vascularized tissues has not been well characterized. In a prospective randomized controlled study including 32 male syngeneic Lewis rats we investigated the capability of the axially vascularized constructs to attract systemically injected bone marrow mononuclear cells (BMMNCs). The underlying mechanism for cell homing was investigated focusing on the role of hypoxia and the SDF1-CXCR4-7 axis. Sixteen animals were used as donors for BMMNCs. The other animals were subjected to implantation of a tissue engineering construct in the subcutaneous groin region. These constructs were axially vascularized either via an arteriovenous loop (AVL, n = 6) or via uninterrupted flow-through vessels (non-AVL, n = 10). BMMNCs were labelled with quantum dots (Qdot® 655) and injected 12 days after surgery either via intra-arterial or intravenous routes. 2 days after cell injection, the animals were sacrificed and examined using fluorescence microscopy. The Qdot® 655 signals were detected exclusively in the liver, spleen, AVL constructs and to a minimal extent in the non-AVL constructs. A significant difference could be detected between the number of labelled cells in the AVL and non-AVL constructs with more cells detected in the AVL constructs specially in central zones ( p <0.0001). The immunohistological analysis showed a significant increase in the absolute expression of HIF-1 in the AVL group in comparison to the non-AVL group. The PCR analysis confirmed a 1.4-fold increase in HIF-1 expression in AVL constructs. Although PCR analysis showed an enhanced expression of CXCR4 and CXCR7 in AVL constructs, no significant differences in SDF1 expression were detected via immunohistological or PCR analysis. At the examined time point, the AVL constructs can attract BMMNCs in a mechanism probably related to the hypoxia associated with a robust tissue formation.

Polymorphism is a key feature of amyloid fibril structures but it remains challenging to explain these variations for a particular sample. Here, we report electron cryomicroscopy-based reconstructions from different fibril morphologies formed by a peptide fragment from an amyloidogenic immunoglobulin light chain. The observed fibril morphologies vary in the number and cross-sectional arrangement of a structurally conserved building block. A comparison with the theoretically possible constellations reveals the experimentally observed spectrum of fibril morphologies to be governed by opposing sets of forces that primarily arise from the β-sheet twist, as well as peptide–peptide interactions within the fibril cross-section. Our results provide a framework for rationalizing and predicting the structure and polymorphism of cross-β fibrils, and suggest that a small number of physical parameters control the observed fibril architectures. Amyloid fibril structures can display polymorphism. Here the authors reveal the cryo-EM structures of several different fibril morphologies of a peptide derived from an amyloidogenic immunoglobulin light chain and present a mathematical analysis of physical factors that influence fibril polymorphism.

A novel stereological framework to generate synthetic three-dimensional cellular material structures using Voronoi tessellations is presented. While conventional investigations of microstructural features rely on costly and often destructive three-dimensional imaging techniques, our method enables the reconstruction of 3D cellular structures from two-dimensional planar-sectional image data. By representing 3D cell architectures through Voronoi tessellations, we obtain an analytical representation requiring only three parameters per cell, ensuring efficient storage and computational processing. Our framework employs a differentiable approximation of Voronoi tessellations combined with a discriminator neural network in an adversarial learning context, enabling gradient-based optimization of tessellation parameters to generate random 3D cellular structures with statistically similar 2D planar sections as observed in measured 2D image data. We demonstrate the framework on image data of various cellular materials including metallic alloys, biological cells, and foam structures. The presented framework shows state-of-the-art capability of stereologically reconstructing 3D cellular microstructures, while introducing a low-parameter representation, preserving physical interpretability, and ensuring computational efficiency.

Orthopaedic disorders represent a significant clinical challenge in avian medicine, affecting both pet and wild birds. B-mode ultrasound (US) examination is well established in small-animal and equine medicine; it has seen limited application in avian medicine thus far. This study aimed to assess the diagnostic efficacy of B-mode US in comparison to radiography (RX) for orthopaedic avian disorders. A total of 55 birds from six orders were assessed clinically, radiologically, and sonographically. Statistical analysis was conducted for the overall cohort (n = 55) and for a fracture subgroup (n = 51). Cohen’s kappa was used to examine diagnostic agreement. Sensitivity, specificity, and positive and negative predictive values were also computed. Additionally, Fisher’s exact test was employed to evaluate the representativeness and interpretability of both techniques. In the overall cohort, US demonstrated higher sensitivity (97.6%) and specificity (100%) than RX (sensitivity 70.7%, specificity 85.7%). In the fracture subgroup, US demonstrated superior sensitivity (97.3%) compared with RX (75.7%) while maintaining high specificity (100%). The agreement between imaging findings and the clinical reference standard was substantial to good (κ = 0.64 for the total cohort, p < 0.05; κ = 0.74 for the fracture subgroup, p < 0.05). No significant differences were identified between the two modalities in terms of representability and interpretability. However, these findings should be interpreted with caution, as US examinations were performed following RX assessment on a non-blinded basis, which may have introduced observational bias. Despite these limitations, B-mode US appears to provide valuable additional diagnostic information and may serve as a complementary imaging modality in the evaluation of avian orthopaedic conditions. In particular, it may be useful for assessing shoulder girdle injuries, inflammatory conditions of the shoulder joint, and fractures of the sternum and keel, as well as for monitoring bone healing following surgical or conservative treatment.

Despite numerous studies presenting advances in tomographic imaging and analysis of lithium ion batteries, graphite-based anodes have received little attention. Weak X-ray attenuation of graphite and, as a result, poor contrast between graphite and the other carbon-based components in an electrode pore space renders data analysis challenging. Here we demonstrate operando tomography of weakly attenuating electrodes during electrochemical (de)lithiation. We use propagation-based phase contrast tomography to facilitate the differentiation between weakly attenuating materials and apply digital volume correlation to capture the dynamics of the electrodes during operation. After validating that we can quantify the local electrochemical activity and microstructural changes throughout graphite electrodes, we apply our technique to graphite-silicon composite electrodes. We show that microstructural changes that occur during (de)lithiation of a pure graphite electrode are of the same order of magnitude as spatial inhomogeneities within it, while strain in composite electrodes is locally pronounced and introduces significant microstructural changes. Tomographic imaging of graphite-based anodes is challenging due to weak X-ray attenuation contrast. Here, the authors use operando propagation-based phase contrast tomography and digital volume correlation to study the electrochemical activity and microstructural dynamics in (silicon−) graphite electrodes.

The paper offers a cursory overview of the state of social scientific knowledge production in East Asia. Conceptually, East Asia is strongly anchored in Eurocentric premises. These have been questioned not only by postcolonial critics but also by the globalization of social reality that has made them theoretically untenable. Steeped in epistemological conservatism and an empiricism inherited from the Anglophone world, East Asia does not yet seem ready to let go of the delusionary certainty these premises provide and of the short-term gratifications the construction of more of the same awards. Given its position in the world, the region should be poised to become a genuine social scientific innovator. But this presupposes coming to terms with an intellectual legacy that has run its course.

ObjectivesThis study aimed to investigate patients’ use of electronic Patient-Reported Outcome Measures (ePROMs) and understand the demographic and clinical factors that may be correlated with patient responses to the BREAST-Q at the preoperative stage of breast cancer. The BREAST-Q is a PROM in questionnaire format, developed and validated to assess satisfaction and quality of life for breast surgery patients.The hypothesis tested is that considering disparities in geography, age and education among responders is essential for capturing a diverse patient population in future Patent-Reported Outcome Measures initiatives, examining how these characteristics are associated with Patent-Reported Outcome Measures utilisation and outcomes.DesignQuantitative descriptive study.SettingElectronic Patient-Reported Outcome Measures were collected between 6 September 2021 and 5 September 2022 from patients recruited from an outpatient clinic at a Plastic- and Breast Surgery Department at a University Hospital in Denmark.ParticipantsParticipants include a total of 629 Danish-speaking women diagnosed with breast cancer and scheduled for breast cancer surgery, with a final participation rate of 468.InterventionPreoperative ePROMs and demographic data were collected between September 2020 and 2021 through patients’ secure national digital post-box.Main outcome measuresDemographic variables of both responders and non-responders were assessed using t-tests, Mann-Whitney U tests and χ2 tests. Linear regression models were employed to determine the demographic variables associated with BREAST-Q subscale scores.ResultsThe response rate for ePROMs was 72.5% with a median age of responders at 62 years. Older patients reported lower breast satisfaction (unadjusted coefficient bu=−0.26 (95% CI −0.44; −0.07), p=0.006) but better physical well-being (adjusted coefficient ba=0.23 (0.08; 0.37), p<0.001). Lower educational achievement was correlated with reduced breast satisfaction and psychosocial and sexual well-being; for example, patients with a master’s/doctoral level education scored 14.29 points higher in psychosocial well-being (95% CI 6.50; 22.07, p<0.001) compared with those with lower secondary education. Cohabiting patients reported psychosocial well-being scores approximately four points higher than those living alone (ba=3.91 (0.06; 7.75), p=0.046). Body mass index (BMI) was negatively associated with sexual well-being, with a 0.75-point decline per additional BMI point (ba=−0.75, (-1.12; −0.37), p<0.001).ConclusionsThe present study demonstrates a positive attitude towards completing BREAST-Q as ePROMs among women diagnosed with breast cancer in the investigated region in Denmark. However, completion rates for ePROMs varied by demographic factors such as age, marital status and access to healthcare. Younger, more educated, married patients with lower BMI who lived near major cities were more likely to report better pretreatment outcomes.

Systemic AL amyloidosis is a rare disease that is caused by the misfolding of immunoglobulin light chains (LCs). Potential drivers of amyloid formation in this disease are post-translational modifications (PTMs) and the mutational changes that are inserted into the LCs by somatic hypermutation. Here we present the cryo electron microscopy (cryo-EM) structure of an ex vivo λ1-AL amyloid fibril whose deposits disrupt the ordered cardiomyocyte structure in the heart. The fibril protein contains six mutational changes compared to the germ line and three PTMs (disulfide bond, N-glycosylation and pyroglutamylation). Our data imply that the disulfide bond, glycosylation and mutational changes contribute to determining the fibril protein fold and help to generate a fibril morphology that is able to withstand proteolytic degradation inside the body. Systemic AL amyloidosis is caused by misfolding of immunoglobulin light chains (LCs) but how post-translational modifications (PTMs) of LCs influence amyloid formation is not well understood. Here, the authors present the cryo-EM structure of an AL amyloid fibril derived from the heart tissue of a patient that is partially pyroglutamylated, N-glycosylated and contains an intramolecular disulfide bond. Based on their structure and biochemical experiments the authors conclude that the mutational changes, disulfide bond and glycosylation determine the fibril protein fold and that glycosylation protects the fibril core from proteolytic degradation.

Background: The growing number of breast cancer survivors underscores the need for tailored follow‐up care, particularly focussing on person‐centred outcomes in surgical follow‐ups. Electronic patient‐reported outcome measures (ePROMs) have the potential to enhance person‐centred care (PCC) by systematically integrating patient perspectives into clinical practice. However, the barriers and facilitators for the utilization of ePROMs in surgical breast cancer follow‐ups remain unclear. Methods: This study utilized a sequential explanatory mixed‐methods design. Quantitative data were collected via a survey among healthcare professionals (HCPs) to assess their familiarity with and perspectives on ePROMs. These findings informed focussed ethnographic qualitative research, including participant observations and interviews, to explore the practical application of ePROMs in clinical practice. Data integration involved a joint display analysis to develop comprehensive insights. Results: While most HCPs (88%) expressed interest in learning more about ePROMs, only 20% agreed that ePROMs improved treatment and care. Time constraints (reported by 56%) and limited system integration (68% were unfamiliar with access via EMR) were reported as key barriers. Nurses prioritized experiential and patient‐specific approaches, often relying on intuition rather than systematic use of ePROMs, whereas surgeons viewed ePROMs as tools for improving resource allocation and surgical outcomes. Knowledge gaps and a lack of organizational support were prevalent, hindering the consistent application of ePROMs in routine care. Conclusions: ePROMs have untapped potential to transform surgical follow‐ups in breast cancer care by aligning clinical practices with person‐centred outcomes. Effective integration requires addressing technical and organizational barriers, enhancing HCPs’ competencies and fostering a supportive culture for systematic ePROM utilization. Tailored implementation strategies are a key to fully realizing the benefits of ePROMs in achieving PCC.