bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning-based risk stratification of preoperative breast biopsies using digital whole slide images
Authors: Boissin Constance , Wang Yinxi , Sharma Abhinav , Weitz Philippe , Karlsson Emelie , Robertson Stephanie , Hartman Johan , Rantalainen Mattias 
Published: June 2024

AbstractBackgroundNottingham histological grade (NHG) is a well established prognostic factor in breast cancer histopathology but has a high inter-assessor variability with many tumours being classified as intermediate grade, NHG2. Here, we evaluate if DeepGrade, a previously developed model for risk stratification of resected tumour specimens, could be applied to risk-stratify tumour biopsy specimens.MethodsA total of 11,955,755 tiles from 1169 whole slide images of preoperative biopsies from 896 patients diagnosed with breast cancer in Stockholm, Sweden, were included. DeepGrade, a deep convolutional neural network model, was applied for the prediction of low- and high-risk tumours. It was evaluated against clinically assigned grades NHG1 and NHG3 on the biopsy specimen but also against the grades assigned to the corresponding resection specimen using area under the operating curve (AUC). The prognostic value of the DeepGrade model in the biopsy setting was evaluated using time-to-event analysis.ResultsBased on preoperative biopsy images, the DeepGrade model predicted resected tumour cases of clinical grades NHG1 and NHG3 with an AUC of 0.908 (95% CI: 0.88; 0.93). Furthermore, out of the 432 resected clinically-assigned NHG2 tumours, 281 (65%) were classified as DeepGrade-low and 151 (35%) as DeepGrade-high. Using a multivariable Cox proportional hazards model the hazard ratio between DeepGrade low- and high-risk groups was estimated as 2.01 (95% CI: 1.06; 3.79).ConclusionsDeepGrade provided prediction of tumour grades NHG1 and NHG3 on the resection specimen using only the biopsy specimen. The results demonstrate that the DeepGrade model can provide decision support to identify high-risk tumours based on preoperative biopsies, thus improving early treatment decisions.
Protein target similarity is positive predictor of in vitro antipathogenic activity: a drug repurposing strategy for Plasmodium falciparum
Authors: Mogire Reagan M. , Miruka Silviane A. , Juma Dennis W. , McNamara Case W. , Andagalu Ben , Burrows Jeremy N. , Chenu Elodie , Duffy James , Ogutu Bernhards R. , Akala Hoseah M. 
Published: June 2024

AbstractDrug discovery is an intricate and costly process. Repurposing existing drugs and active compounds offers a viable pathway to develop new therapies for various diseases. By leveraging publicly available biomedical information, it is possible to predict compounds’ activity and identify their potential targets across diverse organisms. In this study, we aimed to assess the antiplasmodial activity of compounds from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library using in vitro and bioinformatics approaches. We assessed the in vitro antiplasmodial activity of the compounds using blood-stage and liver-stage drug susceptibility assays. We used protein sequences of known targets of the ReFRAME compounds with high antiplasmodial activity (EC50 < 10 uM) to conduct a protein-pairwise search to identify similar Plasmodium falciparum 3D7 proteins (from PlasmoDB) using NCBI protein BLAST. We further assessed the association between the compounds' in vitro antiplasmodial activity and level of similarity between their known and predicted P. falciparum target proteins using simple linear regression analyses. BLAST analyses revealed 735 P. falciparum proteins that were similar to the 226 known protein targets associated with the ReFRAME compounds. Antiplasmodial activity of the compounds was positively associated with the degree of similarity between the compounds’ known targets and predicted P. falciparum protein targets (percentage identity, E value, and bit score), the number of the predicted P. falciparum targets, and their respective mutagenesis index and fitness scores (R2 between 0.066 and 0.92, P < 0.05). Compounds predicted to target essential P. falciparum proteins or those with a druggability index of 1 showed the highest antiplasmodial activity.
Unveiling the entrepreneurial mindset: exploring orientation and intentions among students of prominent engineering disciplines
Authors: Pinto Prakash , Pallikkara Vinish , Pinto Slima , Hawaldar Iqbal Thonse 
Published: June 2024

AbstractThe advent of Industry 4.0 presents a spectrum of challenges for entrepreneurs in India, demanding specific skills and resources. Within this transformative landscape, engineering disciplines assume a pivotal role in navigating the complexities of the new industrial revolution yet pose challenges in instilling entrepreneurial skills. While universities are recognised for fostering entrepreneurial skills, a gap persists in comprehending students’ intentions to pursue entrepreneurship after completing their studies, especially within technical education systems. This emphasises the necessity for a comprehensive examination of variations in entrepreneurial orientation among diverse engineering disciplines. The study employed cross-sectional research and surveyed 370 final-year engineering students from leading engineering colleges in Karnataka, India. The data analysis included Exploratory Factor Analysis (EFA) and Structural Equation Modeling (SEM). The findings demonstrate a significant propensity for entrepreneurship among engineering students, highlighting attributes such as innovativeness, risk-taking, and proactiveness. However, contrary to expectations, the study does not discern distinct entrepreneurial orientations across different engineering disciplines. Importantly, it unveils that college education has minimal influence on students’ entrepreneurial intentions.
Microstructural differences in the cingulum and the inferior longitudinal fasciculus are associated with (extinction) learning
Authors: Nostadt Alina , Schlaffke Lara , Merz Christian J. , Wolf Oliver T. , Nitsche Michael A. , Tegenthoff Martin , Lissek Silke 
Published: June 2024

AbstractCognitive functions, such as learning and memory processes, depend on effective communication between brain regions which is facilitated by white matter tracts (WMT). We investigated the microstructural properties and the contribution of WMT to extinction learning and memory in a predictive learning task. Forty-two healthy participants completed an extinction learning paradigm without a fear component. We examined differences in microstructural properties using diffusion tensor imaging to identify underlying neural connectivity and structural correlates of extinction learning and their potential implications for the renewal effect. Participants with good acquisition performance exhibited higher fractional anisotropy (FA) in WMT including the bilateral inferior longitudinal fasciculus (ILF) and the right temporal part of the cingulum (CNG). This indicates enhanced connectivity and communication between brain regions relevant to learning and memory resulting in better learning performance. Our results suggest that successful acquisition and extinction performance were linked to enhanced structural connectivity. Lower radial diffusivity (RD) in the right ILF and right temporal part of the CNG was observed for participants with good acquisition learning performance. This observation suggests that learning difficulties associated with increased RD may potentially be due to less myelinated axons in relevant WMT. Also, participants with good acquisition performance were more likely to show a renewal effect. The results point towards a potential role of structural integrity in extinction-relevant WMT for acquisition and extinction.
An investigation on the craft of Tianche: traditional timber salt well structures of the Sichuan Basin, China
Authors: Zhu Zhenyu , Li Haiqing , Yu Jingwei 
Published: June 2024

Abstract
This study investigates the craft of Tianche, an ancient towering timber structure used in well salt production in Sichuan Province, China. Originating in the Han Dynasty and maturing in the late Qing Dynasty, Tianches can reach heights of up to 110 m and represent a unique craft and structural system that is rare worldwide, yet remains largely unexplored in scholarly research. The Tianches are under threat due to a lack of maintenance and extinction of the craft. This study aims to document and elucidate the procedure and principles of the Tianche craft to help conserve this heritage. The key question is how to employ traditional craft to assemble over 100-m-tall structures from small-sized logs using pre-industrial technology. The study combines anthropological fieldwork and principles of mechanics to analyze the scientific validity and rationality of traditional crafts. The study reveals the principles of the Tianche craft, including mature craft procedure and reliable binding joints. Its advantages, namely self-locking structure, frictional force transmission, and hollow cylindrical columns, enhance the structure’s strength and stability and are fundamental for constructing 100-m-tall timber structures. Additionally, the study identifies two limitations of the craft: restricted column diameters and the tendency of the inverted dragon member’s tenon to break. This study investigated Tianche timber structures featuring hollow, bundle-like columns with frictional force transmission mechanism, presenting new possibilities beyond mainstream timber structural systems. The findings may contribute to enhancing research on the Tianche craft and could lay the foundation for future conservation practices related to Tianche heritage.
Comparison of manual and artificial intelligence-automated choroidal thickness segmentation of optical coherence tomography imaging in myopic adults
Authors: Lim Zhi Wei , Li Jonathan , Wong Damon , Chung Joey , Toh Angeline , Lee Jia Ling , Lam Crystal , Balakrishnan Maithily , Chia Audrey , Chua Jacqueline , Girard Michael , Hoang Quan V. , Chong Rachel , Wong Chee Wai , Saw Seang Mei , Schmetterer Leopold , Brennan Noel , Ang Marcus 
Published: June 2024

Abstract
Background
Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems.

Methods
Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland–Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement.

Results
A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of − 26.7 µm (95% CI: − 29.7 to − 23.7, P < 0.001) and proportional bias of − 0.090 (P < 0.001).

Conclusion
We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.
Reflections on the benefits and challenges of using co-produced artistic workshops to engage with young people in community settings
Authors: Tinner Laura 
Published: June 2024

Abstract
Background
Despite increased focus on adolescence, young people’s voices are often undervalued and underrepresented in health inequalities research and policy. Through exploring young people’s priorities for their health and their community, we may begin to understand how public health interventions and policies can be more effective and equitable. Engaging with youth using art enables empowerment and self-expression on these complex topics.

Methods
Creative workshops, co-produced with a young artist, were delivered at three youth centres to participants aged 11–18 years (n = 30) in disadvantaged areas of Bristol, UK. Participants engaged in art and were guided by a semi-structured topic guide through focus group discussion. Thematic analysis, supported by the young artist, was used to distil key policy priorities for young people to be delivered to the local authority.

Results
The young people identified a list of key priorities. These were: (1) mental health, (2) feeling ‘forgotten’ as an age group and having safe city spaces to socialise, (3) the need for greater support for their education and career aspirations. I provide a brief summary of these priorities, but the focus of this article is on the critical reflections on this innovative way of engaging with young people about local policy. I provide key learning points for researchers looking to do creative public health work in community settings and involve marginalised young people.

Conclusions
Art is a promising way of engaging with young people in community settings and elevating marginalised voices. Co-producing with a local young artist enriched the project and partially alleviated power imbalances. This approach has potential for involving different groups within local policymaking and priority setting around health inequalities.
Step-by-step optimisation of the radiosynthesis of the brain HDAC6 radioligand [18F]FSW-100 for clinical applications
Authors: Tago Tetsuro , Toyohara Jun 
Published: June 2024

Abstract
Background
Histone deacetylase 6 (HDAC6) is an emerging target for the treatment and diagnosis of proteinopathies. [18F]FSW-100 was recently developed as a promising brain-penetrating radioligand for HDAC6 PET imaging and the process validation of [18F]FSW-100 radiosynthesis for clinical use is complete, but no detailed synthetic strategy nor process optimisation has been reported. Here, we describe the optimisation of several processes in [18F]FSW-100 radiosynthesis, including the 18F-fluorination reaction, semipurification of the 18F-intermediate, and purification of the product by high-performance liquid chromatography (HPLC), to achieve a radiochemical yield (RCY) adequate for clinical applications of the radioligand. Our findings will aid optimisation of radiosynthesis processes in general.

Results
In the 18F-fluorination reaction, the amount of copper reagent was reduced without reducing the nonisolated RCY of the intermediate (50%), thus reducing the risk of copper contamination in the product injection solution. Optimising the solid-phase extraction (SPE) conditions for semipurification of the intermediate improved its recovery efficiency. The addition of anti-radiolysis reagents to the mobile phase for the HPLC purification of [18F]FSW-100 increased its activity yield in radiosynthesis using a high [18F]fluoride radioactivity of approximately 50 GBq. The SPE-based formulation method and additives for the injection solution were optimised, and the resulting [18F]FSW-100 injection solution was stable for over 2 h with a radiochemical purity of greater than 95%.

Conclusions
Of all the reconsidered processes, we found that optimisation of the SPE-based semipurification of the intermediate and of the mobile phase for HPLC purification in particular improved the RCY of [18F]FSW-100, doubling it compared to that of the original protocol. The radioactivity of [18F]FSW-100 synthesized using the optimized protocol was sufficient for multiple doses for a clinical study.
Increase in choroidal thickness after blue light stimulation of the blind spot in young adults
Authors: Hoseini-Yazdi Hosein , Read Scott A. , Collins Michael J. , Bahmani Hamed , Ellrich Jens , Schilling Tim 
Published: June 2024

Abstract
Background
Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness.

Methods
The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460 nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620 nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups.

Results
Compared with sham control (2 ± 1 μm, n = 20) and red light (−1 ± 2 μm, n = 6) stimulation, subfoveal choroidal thickness increased within 60 min after blue light stimulation of the blind spot (7 ± 1 μm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2 μm, p < 0.001) but not in myopes (4 ± 2 μm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation.

Conclusions
These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.
IMA Genome – F19
Authors: Aylward Janneke , Wilson Andi M. , Visagie Cobus M. , Spraker Joseph , Barnes Irene , Buitendag Carla , Ceriani Callin , Del Mar Angel Lina , du Plessis Deanné , Fuchs Taygen , Gasser Katharina , Krämer Daniella , Li WenWen , Munsamy Kiara , Piso Anja , Price Jenna-Lee , Sonnekus Byron , Thomas Chanel , van der Nest Ariska , van Dijk Alida , van Heerden Alishia , van Vuuren Nicole , Yilmaz Neriman , Duong Tuan A. , van der Merwe Nicolaas A. , Wingfield Michael J. , Wingfield Brenda D. 
Published: June 2024

AbstractThe pace at which Next Generation Sequence data is being produced continues to accelerate as technology improves. As a result, such data are increasingly becoming accessible to biologists outside of the field of bioinformatics. In contrast, access to training in the methods of genome assembly and annotation are not growing at a similar rate. In this issue, we report on a Genome Assembly Workshop for Mycologists that was held at the Forestry and Agricultural Biotechnology Institute (FABI) at the University of Pretoria, South Africa and make available the 12 draft genome sequences emanating from the event. With the aim of making the process of genome assembly and annotation more accessible to biologists, we provide a step-by-step guide to both genome assembly and annotation, intended to encourage and empower mycologists to use genome data in their research.
Validation of Methotrexate Intolerance Severity Score (MISS) questionnaire to measure methotrexate intolerance among rheumatoid arthritis Egyptian patients
Authors: Kabil Hagar Ahmed Tawfik , Sherif Nahed Mounir , Elhusseiny Mona Gamal Eldin , Nassif Mary Atef 
Published: June 2024

Abstract
Background
Rheumatoid arthritis (RA) is a systemic autoimmune chronic inflammatory disease, causing progressive disability. Methotrexate (MTX) is the gold standard drug treatment for RA. Long-term use of MTX is associated with intolerance including gastrointestinal effects. In addition, anticipatory, associative, and behavioral symptoms such as anxiety and irritability are also observed which are often inadequately managed, leading to discontinuation of treatment. Methotrexate Intolerance Severity Score (MISS) questionnaire designed to measure MTX intolerance. The work aims to validate the MISS questionnaire Arabic version for the detection of MTX intolerance among Egyptian RA patients to halt the progression of the disease.

Results
A total of 80 patients were involved in this study. Of those, 67 (83.8%) were females with a mean disease duration of 6.9 ± 6.1 years. Forty-eight patients (60%) were intolerant to MTX and 32 patients (40%) were tolerant. Comparison between the tolerant group (n = 32) to MTX and the intolerant group (n = 48) revealed a statistically significant difference between them regarding the DAS28 score and HAQ score. Behavioral intolerance is the predominant factor that directs MTX intolerance.

Conclusion
The MISS questionnaire has a good predictive ability to detect MTX intolerance among Egyptian RA patients. Due to its good reliability, serves as an invaluable tool as it detects anticipatory and associative symptoms.