Mathematics and society reunited: The social aspects of Brouwer's intuitionism.

Brouwer's philosophy of mathematics is usually regarded as an intra-subjective, even solipsistic approach, an approach that also underlies his mathematical intuitionism, as he strived to create a mathematics that develops out of something inner and a-linguistic. Thus, points of connection between Brouwer's mathematical views and his views about and the social world seem improbable and are rarely mentioned in the literature. The current paper aims to challenge and change that. The paper employs a socially oriented prism to examine Brouwer's views on the construction, use, and practice of mathematics. It focuses on Brouwer's views on language, his social interactions, and the importance of group context as they appear in the significs dialogues. It does so by exploring the establishment and dissolution of the significs movement, focusing on Gerrit Mannoury's influence and relationship with Brouwer and analyzing several fragments from the significs dialogues while emphasizing the role Brouwer ascribed to groups in forming and sharing new ideas. The paper concludes by raising two questions that challenge common historical and philosophical readings of intuitionism.

Do hypothetical and actual service distances align for urban fringe parks? An investigation of Shanghai using big data.

In China's transition from rapid urbanization to high-quality development, urban peripheral parks are increasingly crucial for ecological services and quality of life. However, a disparity persists between their intended function and actual usage, a common occurrence in megacities of China. This study aims to identify the actual service distance and accessibility of parks in fringe areas, using the southwestern sector of Shanghai's main urban fringe as an example. By utilizing mobile location data, it explores the multilevel service attributes of urban fringe parks. Analyzing spatial characteristics from the perspectives of clustering distances and life circle service capabilities, it concludes that: 1) fringe parks exhibit lower service capacities compared to central ones, mainly providing routine services; 2) fixed service range models are inadequate, especially for fringe parks; and 3) community and district-level parks have comparable service distances, highlighting the need to enhance district-level parks. This research aims to optimize park site selection and functions in urban peripheries, providing insights for sustainable planning.

A case of minimum invasive debranch thoracic endovascular aortic repair for isolated left vertebral artery: complete revascularization without artificial vessels via a single small incision.

Isolated left vertebral artery (ILVA) is one of the most frequent vertebral abnormalities. When performing thoracic endovascular aortic repair (TEVAR), the ILVA may have to be closed depending on the position of the stent graft; in these cases, the decision to reconstruct the ILVA depends on the state of cerebral blood flow. Here, we report a case of a 68-year-old male, in whom the Willis arterial circle was incomplete; we therefore performed a reconstructive method during zone 2-landing TEVAR that ensured ILVA and left subclavian artery blood flow without the use of artificial vessels. Only one supraclavicular incision was required for reconstruction. This method has some procedural difficulties; however, it does not use artificial blood vessels and can be performed with a single incision.

Reconfiguring Shortest Paths in Graphs.

Reconfiguring two shortest paths in a graph means modifying one shortest path to the other by changing one vertex at a time so that all the intermediate paths are also shortest paths. This problem has several natural applications, namely: (a) repaving road networks, (b) rerouting data packets in a synchronous multiprocessing setting, (c) the shipping container stowage problem, and (d) the train marshalling problem. When modelled as graph problems, (a) is the most general case while (b), (c), (d) are restrictions to different graph classes. We show that (a) does not admit polynomial-time algorithms (assuming P ≠ NP ), even for relaxed variants of the problem (assuming P ≠ PSPACE ). For (b), (c), (d), we present polynomial-time algorithms to solve the respective problems. We also generalize the problem to when at most k (for a fixed integer k ≥ 2 ) contiguous vertices on a shortest path can be changed at a time.

An ultra-sensitive suboptimal protospacer adjacent motif enhanced rolling circle amplification assay based on CRISPR/Cas12a for detection of miR-183.

Introduction: MicroRNAs (miRNAs) have been recognized as promising diagnostic biomarkers for Diabetic Retinopathy (DR) due to their notable upregulation in individuals with the condition. However, the development of highly sensitive miRNAs assays for the rapid diagnosis of DR in clinical settings remains a challenging task. Methods: In this study, we introduce an enhanced CRISPR/Cas12a assay, leveraging suboptimal PAM (sPAM)-mediated Cas12a trans-cleavage in conjunction with rolling circle amplification (RCA). sPAM was found to perform better than canonical PAM (cPAM) in the detection of Cas12a-mediated ssDNA detection at low concentrations and was used instead of canonical PAM (cPAM) to mediate the detection. The parameters of reactions have also been optimized. Results and discussion: In comparison with cPAM, sPAM has higher sensitivity in the detection of ssDNA at concentrations lower than 10 pM by Cas12a. By replacing cPAM with sPAM in the padlock template of RCA, ultra-high sensitivity for miR-183 detection is achieved, with a detection limit of 0.40 aM. within 25 min and a linear range spanning from 1 aM. to 1 pM. Our assay also exhibits exceptional specificity in detecting miR-183 from other miRNAs. Furthermore, the applicability of our assay for the sensitive detection of miR-183 in clinical serum samples is also validated. This study introduces a groundbreaking assay with excellent performance through a simple modification, which not only addresses existing diagnostic challenges, but also opens exciting new avenues for clinical diagnosis in the realm of DR.

RNA transcription assisted universal CRISPR/Cas12a system for programmable analysis of multiple colorectal cancer-associated microRNAs.

Accurate analysis of multiple microRNA (miRNA) levels is significantly valuable for early diagnosis of colorectal cancer noninvasively considering the miRNA expression is highly relevant to the occurrence and progression of cancer. However, the low abundance and high sequence homology of miRNAs make their precise determination extremely challenging. Here, we developed a universal and programmable diagnostic strategy allowing for analyzing multiple colorectal cancer-associated miRNAs. The system combined sequentially programmable rolling circle transcription (RCT) and the CRISPR/Cas12a system with high trans-cleavage activity to achieve highly sensitive and specific detection of four target miRNAs. Owing to the remarkable performance of universal RCT-Cas12a strategy, this biosensor could detect miR-21, miR-17, miR-31 and miR-92a with a LOD of 2.1, 1.6, 3.7 and 1.0 pM, respectively. This strategy had a unique advantage in distinguishing human normal colon epithelial cells lines (NCM460) from human colon cancer cells (HT29). In particular, the designed system exhibited superior analytical capability in distinguishing paracancerous and colorectal cancer tissues from patients undergoing colorectal cancer surgery. This arbitrarily programmable, scalable, fast and specific strategy potentially offered an attractive alternative to handle varied challenges encountered with CRISPR-based systems, and held immense promise in scientific research and clinical applications.

Assessing the current role of AP and Bernageau view radiographs in measurement of glenoid bone loss in patients with recurrent shoulder dislocation: correlation with computed tomography, magnetic resonance imaging, and arthroscopy.

BACKGROUND: Evaluation of glenoid bone loss following recurrent anterior shoulder dislocations is normally performed using cross sectional imaging. OBJECTIVES: To assess how anteroposterior (AP) and Bernageau view radiographs compare to computed tomography (CT), magnetic resonance imaging (MRI) and arthroscopy for evaluating glenoid bone loss in patients with recurrent anterior shoulder dislocation. MATERIALS AND METHODS: A prospective observational study was performed on 32 patients over two years at a tertiary orthopedic center. The loss of sclerotic glenoid rim (LSGL) on AP radiograph and the percentage relative glenoid bone loss on the Bernageau radiograph were assessed. The percentage glenoid bone loss and anterior straight line (ASL) were calculated using a best fit en face circle method using CT and MRI. Percentage glenoid bone loss was also calculated during arthroscopy in multiples of 5%. RESULTS: In our study, 90.6% (29) patients were males, while only 9.4% (3) were females. This can be attributed to the involvement of the males in outdoor activities and sports. Also, the maximum number of patients were found to belong to 21-30 years of age, with the mean age being 28.66 years. Of the 32 patients, loss of sclerotic glenoid line (LSGL) on AP radiographs correlated with glenoid bone loss on cross-sectional imaging in 27 patients. Three patients had equivocal LSGL and 2 patients with glenoid bone loss on CT did not demonstrate LSGL. The difference between the two modalities was not statistically significant (p value = 0.002). The glenoid bone loss on Bernageau view correlated with glenoid bone loss on cross sectional imaging in all but one patient. The bone loss as evaluated by radiograph Bernageau view was found to have strong correlation (correlation coefficient r = 0.948, p value < 0.0001). CONCLUSION: AP and Bernageau radiographic views for anterior shoulder dislocations demonstrate good correlation with glenoid bone loss on cross-sectional imaging. They may also be used as an adjunct to predict overall bone loss on CT and at arthroscopy.

A New Strategy for Ultrasensitive Detection Based on Target microRNA-Triggered Rolling Circle Amplification in the Early Diagnosis of Alzheimer's Disease.

There is an urgent need to accurately quantify microRNA (miRNA)-based Alzheimer's disease (AD) biomarkers, which have emerged as promising diagnostic biomarkers. In this study, we present a rapid and universal approach to establishing a target miRNA-triggered rolling circle amplification (RCA) detection strategy, which achieves ultrasensitive detection of several targets, including miR-let7a-5p, miR-34a-5p, miR-206-3p, miR-9-5p, miR-132-3p, miR-146a-5p, and miR-21-5p. Herein, the padlock probe contains three repeated signal strand binding regions and a target miRNA-specific region. The target miRNA-specific region captures miRNA, and then the padlock probe is circularized with the addition of T4 DNA ligase. Subsequently, an RCA reaction is triggered, and RCA products containing multiple signal strand binding regions are generated to trap abundant fluorescein-labeled signal strands. The addition of exonuclease III (Exo III) causes signal strand digestion and leads to RCA product recycling and liberation of fluorescein. Ultimately, graphene oxide (GO) does not absorb the liberated fluorescein because of poor mutual interaction. This method exhibited high specificity, sensitivity, repeatability, and stability toward let-7a, with a detection limit of 19.35 fM and a linear range of 50 fM to 5 nM. Moreover, it showed excellent applicability for recovering miRNAs in normal human serum. Our strategy was applied to detect miRNAs in the plasma of APP/PS1 mice, demonstrating its potential in the diagnosis of miRNA-associated disease and biochemical research.

Molar incisor hypomineralization (MIH): The "Why, What and How" of decision making for orthodontists.

Molar-incisor hypomineralization (MIH) presents a significant clinical challenge in orthodontics, with its complex etiology, variable presentation, and profound impact on enamel homeostasis. Utilizing Simon Sinek's "Golden Circle" method, this article systematically explores the implications of MIH within orthodontic practice. The "Why" emphasizes the critical need for orthodontists to understand MIH, given its prevalence and potential to disrupt treatment outcomes. MIH affects up to 40.2% of the global population, and its association with increased caries risk, hypersensitivity, and restorative failures necessitates an informed approach to management. The "What" section addresses the importance of recognizing the phenotypic variability of MIH and its influence on oral health-related quality of life. MIH impacts social and psychological well-being, particularly when anterior teeth are involved, and complicates orthodontic treatment due to challenges in bonding, banding, and restorative protocols. The "How" provides practical guidelines for orthodontic management, including diagnostic considerations, tooth restoration strategies, and the complexities of first permanent molar extractions. Strategic planning is essential to avoid complications such as mesial drift, overeruption, or space loss, with a multidisciplinary approach often required. This article highlights the importance of long-term monitoring and patient-centered care in managing MIH-affected teeth, underscoring the evolving nature of clinical protocols. By framing the discussion through the Golden Circle, this critical review offers a structured and impactful approach to understanding and addressing MIH within orthodontic contexts, aiming to enhance treatment outcomes and patient quality of life.

CRISPR/Cas12a-Based Indirect Competitive Enzyme-Linked Immunosorbent Assay for Sensitive Detection of Ochratoxin A.

The high toxicity and widespread contamination of ochratoxin A (OTA) make it urgent to develop a sensitive method to detect trace OTA in complex food matrices. Herein, an indirect competitive enzyme-linked immunosorbent assay (icELISA)-based on the CRISPR/Cas12a system is described. DNA amplicons with multiple activation sequences of the CRISPR/Cas12a system were pre-prepared to improve detection sensitivity. In the absence of OTA, streptavidin-mediated biotinylated DNA amplicons were captured by the biotinylated secondary antibody on the microplate. The captured DNA amplicons activated the CRISPR/Cas12a system, which thereby effectively cleaved the reporter DNA, producing strong fluorescence. The presence of OTA led to a decrease in DNA amplicons on the microplate, resulting in a decrease in activated Cas12a and ultimately a drop in fluorescence intensity. OTA in food matrices at nanogram per milliliter levels can be detected. Therefore, the new method has great potential in monitoring OTA.

Madura foot: How MRI aids in diagnosis.

A 46-year-old farmer living in a rural area, who sustained an injury to his left foot 10 years ago, consulted due to progressive swelling of the same foot. An MRI revealed the "dot-in-circle" sign, suggestive of mycetoma of the foot, also known as Madura foot. This condition primarily affects soft tissues and bones and can occasionally lead to potentially severe visceral complications. Foot involvement is predominant, observed in 80% of cases.

Axial compression performances and bearing capacity prediction of self-compacting fly ash concrete filled circle steel tube columns.

To solve the problem of a large amount of fly ash accumulation and study the axial compression and bearing capacity prediction of the self-compacting fly ash concrete filled circle steel tube (SCCFST) columns, eight specimens are designed to explore the impact of concrete strength grade, internal structural measures, and additional parameters. The stress, progression of deformation, and failure mode of each specimen are observed during the loading process. The load-displacement curves, load-strain curves, characteristic load and displacement, ductility, and stiffness degradation are analyzed. The findings revealed that shear deformation occurred predominantly in the middle and upper portions of the steel tubes. Enhancing the strength of the concrete or adopting internal structural measures could increase the bearing capacity and ductility of the specimens. The peak load and ductility could be increased by up to 17.6 and 53.6%, respectively. The proposed unified calculation equation for the axial compression bearing capacity of SCCFST columns demonstrates notable reliability and precision. Furthermore, these tests offer valuable references for the engineering application of various forms of SCCFST columns, which are of significant importance in practical engineering.

Advances in DNA nanotechnology for chronic wound management: Innovative functional nucleic acid nanostructures for overcoming key challenges.

Chronic wound management is affected by three primary challenges: bacterial infection, oxidative stress and inflammation, and impaired regenerative capacity. Conventional treatment methods typically fail to deliver optimal outcomes, thus highlighting the urgency to develop innovative materials that can address these issues and improve efficacy. Recent advances in DNA nanotechnology have garnered significant interest, particularly in the field of functional nucleic acid (FNA) nanomaterials, owing to their exceptional biocompatibility, programmability, and therapeutic potential. Among them, FNAs with unique nanostructures have garnered considerable attention. First, they inherit the biological properties of FNAs, including biocompatibility, reactive oxygen species (ROS)-scavenging capabilities, and modulation of cellular functions. Second, based on a precise design, these nanostructures exhibit superior physical properties, stability, and cellular uptake. Third, by leveraging the programmability of DNA strands, FNA nanostructures can be customized to accommodate therapeutic nucleic acids, peptides, and small-molecule drugs, thereby enabling a stable and controlled drug delivery system. These unique characteristics enable the use of FNA nanostructures to effectively address the major challenges in chronic wound management. This review focuses on various FNA nanostructures, including tetrahedral framework nucleic acids (tFNAs), DNA hydrogels, DNA origami, and rolling-circle amplification (RCA) DNA assembly. Additionally, a summary of recent advancements in their design and application for chronic wound management as well as insights for future research in this field are provided.

Close Relations, Practitioners or Social Networks: What Affects the Selection of Infant Formula Products?

This study examines which factors influence the preferences of mothers seeking advice on the use of infant formula in feeding practices. The effects of their close social circle, medical professionals and social network forums on feeding choices were evaluated. Data were collected from 638 questionnaires from mothers and were statistically analyzed. Our findings suggest that age may influence the preference to seek advice from a close social circle over consulting with medical professionals (p-value = 0.019 < 0.05). The educational level and the number of children impact the preferences of using infant formula over combining it with breastfeeding (p-value = 0.000 < 0.05 and p-value = 0.004 < 0.05, respectively). The research contributes to the understanding of the complex interplay between various demographic and socioeconomic factors and the decision-making process of mothers based on multiple social and digital sources of influence. The research presents valuable insights for healthcare policymakers and professionals in supporting mothers and providing them with up-to-date information. Feeding information can be distributed through all the communication channels that were examined in this study to benefit different socio-economic groups and to contribute to the well-being of infants in the long-run.

Diverse Head-to-Tail Sequences in the Circular Genome of Human Bocavirus Genotype 1 among Children with Acute Respiratory Infections Implied the Switch of Template Chain in the Rolling-Circle Replication Model.

Head-to-tail sequences have been reported in human bocavirus (HBoV) 1-4. To reveal their features and functions, HBoV DNA was screened among respiratory specimens from pediatric patients with an acute respiratory infection (ARI) between April 2020 and December 2022, followed by HBoV genotyping. Head-to-tail sequences were detected using nested PCR, TA cloning, and Sanger sequencing, and these findings were confirmed by mNGS and amplicon sequencing. The secondary structure was predicted using the Mfold web server. The results indicated that head-to-tail sequences were detected in 42 specimens through TA cloning from 351 specimens positive for HBoV1 DNA, yielding 92 sequences into 32 types and 2 categories. Additionally, head-to-tail sequences were detected in 16 specimens by amplicon sequencing, yielding 60 sequences categorized into 23 types. The 374nt type, detected in 13 specimens, contains variants 374a and 374b, which differ in the unpaired loop regions of the palindrome or complementary reverse sequences, implying a switch of template chains during the replication process. The mNGS results in three specimens confirmed the presence of circular genome in copies below 1%. In conclusion, head-to-tail sequences of HBoV1 were common in children with ARI and were highly diverse in length and sequences. The variants may be generated by the switch of the template chain in the rolling-circle replication model.

A one-pot isothermal Fluorogenic Mango II arrays-based assay for label-free detection of miRNA.

The capability to detect a small number of miRNAs in clinical samples with simplicity, selectivity, and sensitivity is immensely valuable, yet it remains a daunting task. Here, we described a novel Mango II aptamers-based sensor for the one-pot, sensitive and specific detection of miRNAs. Target miRNA-initiated mediated catalyzed hairpin assembly (CHA) would allow for the production of plenty of DNA duplexes and the formation of the complete T7 promoter, motivating the rolling circle transcription (RCT). Then, the subsequent RCT process efficiently generates a huge number of repeating RNA Mango II aptamers, brightened by the incorporation of fluorescent dye TO1-B for miRNA quantification, realizing label-free and high signal-to-background ratio. Moreover, this assay possesses a remarkable ability to confer high selectivity, enabling the distinction of miRNAs among family members with mere 1- or 2- nucleotide (nt) differences. By employing the proposed assay, we have successfully achieved a sensitive evaluation of miR-21 content in diverse cell lines and clinical serum samples. This offers a versatile approach for the sensitive assay of miRNA biomarkers in molecular diagnosis.

Ingenious dual-circle DNA walker-mediated electrochemical biosensor for rapid and ultrasensitive detection of microRNA.

In this work, an ingenious dual-circle DNA walker (DCDW) with pretty fast walking speed and high amplification efficiency was developed for rapid and ultrasensitive electrochemical detection of microRNA-221 (miRNA-221) related to liver cancer, combined with the toehold-mediated strand-displacement reactions (TSDRs). Impressively, compared with the traditional DNA walker, the DCDW with unique double-stranded interlocked DNA nanostructure not only possesses higher stability, flexibility, and anti-entanglement ability, but also enables more functional domain in a smaller area, thereby enhancing the local concentration, which can greatly improve the working efficiency. As a validation, the electrochemical biosensor realized rapid and ultrasensitive detection of miRNA-221 with a reaction time of 15 min and detection limit down to 1.9 aM, and had been applied in MHCC97L and HeLa cancer cell lysates, thus providing an innovative insight to design intelligent functional interlocked DNA walkers for ultimate application in the construction of biosensing platform and miRNA detection in biological sample.

Equity and efficiency of health resource allocation in the Chengdu-Chongqing Economic Circle of China.

Objective: This study aimed to evaluate the fairness and efficiency of health resource allocation (HRAE) in Chengdu-Chongqing Economic Circle after the new healthcare reform. This study also aimed to identify existing problems, providing empirical evidence for the government to formulate regional health plans scientifically and reasonably. Methods: The fairness of health resource allocation was analyzed using the Gini coefficient, Theil index, and agglomeration degree from population and geographical area perspectives. The three-stage data envelopment analysis and the Malmquist productivity index were used to analyze HRAE from static and dynamic perspectives. Results: The Gini coefficient for population allocation in Chengdu-Chongqing Economic Circle was 0.066-0.283, and the Gini coefficient for geographical area allocation was 0.297-0.469. The contribution rate within a region was greater than that between regions, and health resources were mainly concentrated in economically developed core areas. The overall fairness of Chengdu Economic Circle was relatively better than that of Chongqing Economic Circle. Moreover, the adjusted mean technical efficiency was 0.806, indicating room for HRAE improvement in Chengdu-Chongqing Economic Circle. Stochastic Frontier Analysis found that different environmental variables have varying degrees of impact on HRAE. The adjusted mean total factor productivity change (Tfpch) was 1.027, indicating an overall upward trend in HRAE since the new healthcare reform. However, scale efficiency change (Sech) (0.997) limited the improvement of Tfpch. Conclusion: The fairness of health resources allocated by population was better than that allocated by geographical area. The unfairness of health resources mainly stemmed from intra-regional differences, with considerable health resources concentrated in core areas. Over the past 13 years, HRAE has improved but exhibited spatial heterogeneity and Sech-hindered productivity improvement. The study recommends strengthening regional cooperation and sharing to promote the integrated and high-quality development of the health and well-being in Chengdu-Chongqing Economic Circle.

Circle of Vieussens: Its Importance in the Presence of Significant Coronary Artery Stenosis in a 26-Year-Old Female With Kawasaki Disease.

In patients with coronary artery disease (CAD), collateral circulation aids in sustaining myocardial perfusion and cardiac function. The circle of Vieussens is a rare collateral pathway between the right coronary artery and the left anterior descending artery (LAD) that plays a significant role specifically in patients with chronic total occlusions (CTOs). This article presents a unique case of the circle of Vieussens in a 26-year-old Asian female with a history of Kawasaki disease and CTO of the proximal LAD. Despite the CTO, the patient remains asymptomatic and maintains normal left ventricular function, attributed to an effective collateral network including a right-to-left arterial ring providing TIMI 3 flow. The case illustrates the crucial role of collateral circulation in managing complex coronary anomalies and underscores the need for comprehensive cardiac evaluations in patients with Kawasaki disease. This finding also highlights the potential of the circle of Vieussens as a lifesaving alternate conduit in severe CAD scenarios.

Immobilization coupling with aptamer assisted dual cycle amplification for sensitive sEVs isolation and analysis.

Precise identification of small extracellular vesicles (sEVs) is crucial for improving disease diagnosis and treatments, such as bladder cancer. However, accurate isolation and simultaneously quantification of sEVs remain a huge challenge. We have introduced a new technique that combines immobilization with aptamer-assisted dual cycle amplification to isolate and analyze sEVs with high sensitivity. In this method, the CD9 protein antibody is attached to the plate's surface for the initial identification of sEVs, while an aptamer probe is used to detect the exosomal surface protein CD63. We have created an sEVs-surface method that combines target recognition initiated signal recycling and rolling circle amplification (RCA) for signal amplification. This approach allows for the "AND" logic analysis of dual biomarkers, enabling both sEVs quantification and tracing. The proposed approach has a broad detection range and a low limit of detection. Moreover, the established method showed good stability in detecting sEVs with a low coefficient of variation. Our method can effectively isolate certain sEVs and accurately identify them, making it suitable for many uses in biological science, biomedical engineering, and personalized medicine.