Miracle-dz/UniFAR-FTUs huggingface dataset:
Prime Editing for Inherited Retinal Diseases

Inherited retinal diseases (IRDs) are chronic, hereditary disorders that lead to progressive degeneration of the retina. Disease etiology originates from a genetic mutation—inherited or de novo—with a majority of IRDs resulting from point mutations. Given the plethora of IRDs, to date, mutations that cause these dystrophies have been found in approximately 280 genes. However, there is currently only one FDA-approved gene augmentation therapy, Luxturna (voretigene neparvovec-rzyl), available to patients with RPE65-mediated retinitis pigmentosa (RP). Although clinical trials for other genes are underway, these techniques typically involve gene augmentation rather than genome surgery. While gene augmentation therapy delivers a healthy copy of DNA to the cells of the retina, genome surgery uses clustered regularly interspaced short palindromic repeats (CRISPR)-based technology to correct a specific genetic mutation within the endogenous genome sequence. A new technique known as prime editing (PE) applies a CRISPR-based technology that possesses the potential to correct all twelve possible transition and transversion mutations as well as small insertions and deletions. EDIT-101, a CRISPR-based therapy that is currently in clinical trials, uses double-strand breaks and nonhomologous end joining to remove the IVS26 mutation in the CEP290 gene. Preferably, PE does not cause double-strand breaks nor does it require any donor DNA repair template, highlighting its unparalleled efficiency. Instead, PE uses reverse transcriptase and Cas9 nickase to repair mutations in the genome. While this technique is still developing, with several challenges yet to be addressed, it offers promising implications for the future of IRD treatment.
Endorsing Sustainable Enterprises Among Promising Entrepreneurs: A Comparative Study of Factor-Driven Economy and Efficiency-Driven Economy

Understanding business trails among promising aspirants may contribute to an actual motive for diminishing ecological tracks and escort to developing devotion toward deciding intentions across various entrepreneurial types and tiers solely from the sustainability domains. Therefore, this study endeavors to comprehend and seek to employ the Theory of Planned Behavior (TPB) to inspect the relationship between antecedents on sustainable enterprise intention and sustainable value creation. In this study, we used the convenience sampling method and the quantitative data of 1,070 respondents from Pakistan and China and applied a SmartPLS structural equation model and partial least square path modeling by mediational and multigroup analyses. Findings divulge that R2 (79.8%) value in the Pakistan sample of attitudes to sustainability, perceived entrepreneurial desirability (PED), and perceived entrepreneurial feasibility (PEF) was comparatively higher than in China. The R2 (75.6%) variance value on sustainable entrepreneurial intentions (SEI) was recorded higher in the Pakistani sample. However, the relationship of environmental values, self-efficacy, and extrinsic and intrinsic rewards show positive and significant mediational effects on both the economies of SEI. The findings disclosed an inconsistent character of extrinsic rewards, general self-efficacy, and job security depict negative significant impacts of aspirations on sustainable entrepreneurship (SE) among promising entrepreneurs on sustainability enterprises in both Pakistan and China. This study extends on existing entrepreneurship literature. Results supported the designed hypothesis and played a significant role in shedding light on an individual trait underpinning a career in a sustainable business start-up. The study looks at the issue from the viewpoint of sustainability domains. It seeks to determine the individual PED, PEF, and attitude toward sustainable entrepreneurship (ATSE) as the mediational variables. The study highlights the importance of work values in pursuing sustainability-oriented entrepreneurship programs for promising aspirants to improve their entrepreneurial skills and knowledge podium, which will encourage them to become sustainable future entrepreneurs. Furthermore, the study provides understandings for ratifying sustainable openings and debates the potential paths for sustainable business growth and opportunities among nascent entrepreneurs in both economies.
Determinants of Intention to Use Artificial Intelligence-Based Diagnosis Support System Among Prospective Physicians

Background: This study aimed to develop a theoretical model to explore the behavioral intentions of medical students to adopt an AI-based Diagnosis Support System. Methods: This online cross-sectional survey used the unified theory of user acceptance of technology (UTAUT) to examine the intentions to use an AI-based Diagnosis Support System in 211 undergraduate medical students in Vietnam. Partial least squares (PLS) structural equational modeling was employed to assess the relationship between latent constructs. Results: Effort expectancy (β = 0.201, p < 0.05) and social influence (β = 0.574, p < 0.05) were positively associated with initial trust, while no association was found between performance expectancy and initial trust (p > 0.05). Only social influence (β = 0.527, p < 0.05) was positively related to the behavioral intention. Conclusions: This study highlights positive behavioral intentions in using an AI-based diagnosis support system among prospective Vietnamese physicians, as well as the effect of social influence on this choice. The development of AI-based competent curricula should be considered when reforming medical education in Vietnam.
A Multivariate Diagnostic Model Based on Urinary EpCAM-CD9-Positive Extracellular Vesicles for Prostate Cancer Diagnosis

Introduction Prostate cancer (PCa) is one of the most frequently diagnosed cancers and the leading cause of cancer death in males worldwide. Although prostate-specific antigen (PSA) screening has considerably improved the detection of PCa, it has also led to a dramatic increase in overdiagnosing indolent disease due to its low specificity. This study aimed to develop and validate a multivariate diagnostic model based on the urinary epithelial cell adhesion molecule (EpCAM)-CD9–positive extracellular vesicles (EVs) (uEVEpCAM-CD9) to improve the diagnosis of PCa. Methods We investigated the performance of uEVEpCAM-CD9 from urine samples of 193 participants (112 PCa patients, 55 benign prostatic hyperplasia patients, and 26 healthy donors) to diagnose PCa using our laboratory-developed chemiluminescent immunoassay. We applied machine learning to training sets and subsequently evaluated the multivariate diagnostic model based on uEVEpCAM-CD9 in validation sets. Results Results showed that uEVEpCAM-CD9 was able to distinguish PCa from controls, and a significant decrease of uEVEpCAM-CD9 was observed after prostatectomy. We further used a training set (N = 116) and constructed an exclusive multivariate diagnostic model based on uEVEpCAM-CD9, PSA, and other clinical parameters, which showed an enhanced diagnostic sensitivity and specificity and performed excellently to diagnose PCa [area under the curve (AUC) = 0.952, P < 0.0001]. When applied to a validation test (N = 77), the model achieved an AUC of 0.947 (P < 0.0001). Moreover, this diagnostic model also exhibited a superior diagnostic performance (AUC = 0.917, P < 0.0001) over PSA (AUC = 0.712, P = 0.0018) at the PSA gray zone. Conclusions The multivariate model based on uEVEpCAM-CD9 achieved a notable diagnostic performance to diagnose PCa. In the future, this model may potentially be used to better select patients for prostate transrectal ultrasound (TRUS) biopsy.
Multiple Survival Outcome Prediction of Glioblastoma Patients Based on Multiparametric MRI

Purpose Construction of radiomics models for the individualized estimation of multiple survival stratification in glioblastoma (GBM) patients using the multiregional information extracted from multiparametric MRI that could facilitate clinical decision-making for GBM patients. Materials and Methods A total of 134 eligible GBM patients were selected from The Cancer Genome Atlas. These patients were separated into the long-term and short-term survival groups according to the median of individual survival indicators: overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). Then, the patients were divided into a training set and a validation set in a ratio of 2:1. Radiomics features (n = 5,152) were extracted from multiple regions of the GBM using multiparametric MRI. Then, radiomics signatures that are related to the three survival indicators were respectively constructed using the analysis of variance (ANOVA) and the least absolute shrinkage and selection operator (LASSO) regression for each patient in the training set. Based on a Cox proportional hazards model, the radiomics model was further constructed by combining the signature and clinical risk factors. Results The constructed radiomics model showed a promising discrimination ability to differentiate in the training set and validation set of GBM patients with survival indicators of OS, PFS, and DSS. Both the four MRI modalities and five tumor subregions have different effects on the three survival indicators of GBM. The favorable calibration and decision curve analysis indicated the clinical decision value of the radiomics model. The performance of models of the three survival indicators was different but excellent; the best model achieved C indexes of 0.725, 0.677, and 0.724, respectively, in the validation set. Conclusion Our results show that the proposed radiomics models have favorable predictive accuracy on three survival indicators and can provide individualized probabilities of survival stratification for GBM patients by using multiparametric and multiregional MRI features.
An Overview of in vivo Functions of Chondroitin Sulfate and Dermatan Sulfate Revealed by Their Deficient Mice

Chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) are covalently attached to specific core proteins to form proteoglycans in their biosynthetic pathways. They are constructed through the stepwise addition of respective monosaccharides by various glycosyltransferases and maturated by epimerases as well as sulfotransferases. Structural diversities of CS/DS and HS are essential for their various biological activities including cell signaling, cell proliferation, tissue morphogenesis, and interactions with a variety of growth factors as well as cytokines. Studies using mice deficient in enzymes responsible for the biosynthesis of the CS/DS and HS chains of proteoglycans have demonstrated their essential functions. Chondroitin synthase 1-deficient mice are viable, but exhibit chondrodysplasia, progression of the bifurcation of digits, delayed endochondral ossification, and reduced bone density. DS-epimerase 1-deficient mice show thicker collagen fibrils in the dermis and hypodermis, and spina bifida. These observations suggest that CS/DS are essential for skeletal development as well as the assembly of collagen fibrils in the skin, and that their respective knockout mice can be utilized as models for human genetic disorders with mutations in chondroitin synthase 1 and DS-epimerase 1. This review provides a comprehensive overview of mice deficient in CS/DS biosyntheses.
A Flipped Inquiry-based Learning with Mobility to Improving Students’ Learning Performance in Science: A Comparative Study

The present study examines the differential impact of studying in an innovative learning approach, flipped inquiry-based learning with mobility (FILM) setting, as compared to a hands-on inquiry-based learning (HIL), and traditional learning (TL) setting on science learning performance regarding scientific conceptual understanding. Participants were eleventh-grade students (N = 79), enrolled in physics course in a public secondary school in northeastern region of Thailand. They were divided into the three groups and randomly assigned according to one of the three experimental conditions (TL n = 25, HIL n = 23, FILM n = 31). The results showed that conceptual learning performance on liquid pressure was superior in the FILM group as compared to other learning settings (Cohens' d = 3.35), HIL (Cohens' d = 0.64) and TL (Cohens' d = 0.99). Students in the HIL setting had a higher conceptual learning performance as compared to the TL setting. This finding suggest that the FILM setting could be a promising way of enhancing high school students’ learning performance in science.
The Value of Data and Other Non-traditional Scholarly Outputs in Academic Review, Promotion, and Tenure in Canada and the United States

Academics are regularly involved in a wide range of activities spanning research, teaching and service, and the breadth of necessary outputs for review, promotion, and tenure (RPT) in each category only continues to grow. In linguistics, for example, research increasingly relies on the creation and management of datasets and on research software used to process these data. How do faculty manage their academic careers in the face of such growing sets of demands? Although we know that discussions of research assessment across the academy, including in the linguistics community, are increasingly recognizing the need to value the creation of outputs beyond research published in peerreviewed journals, it is not clear whether these discussions have made their way into formal assessment structures. By analyzing the extent to which non-traditional outputs, including data and software, are mentioned in the RPT documents of a representative set of 129 universities from the United States and Canada, this chapter offers empirical evidence from across many disciplines of which types of faculty work are recognized in the RPT processes, and which are not. We confirm that traditional outputs such as peer-reviewed journal articles, book chapters and monographs are mentioned almost universally, whereas data-related items such as datasets and databases are mentioned only by a fraction of institutions. We find that research-intensive institutions acknowledge more types of research outputs in general, whereas institutions that focus more on undergraduate and master’s degree programs tend to mention fewer forms of scholarship in their RPT guidelines. Within research-intensive institutions, units from the life sciences present a greater range of outputs in the guidelines offered to faculty, including the 15% that explicitly mention data-related outputs. In contrast, none of the academic units in mathematics and physical and social sciences in our sample recognize data-related outputs, and generally recognize fewer forms. Overall, we conclude that many current structures for faculty assessment do not explicitly recognize the increasing complexity and demands of faculty work. Acknowledgements We would like to acknowledge the critically important work of Carol Muñoz Nieves, who spent hours poring over the documents to identify and classify the outputs found here. We would also like to thank Kendal Crawford and Lisa Matthias for their relentless efforts to collect RPT documents necessary to enable this work in the first place, as well as the editors, two anonymous reviewers, and Daniella Lowenberg for their thoughtful feedback on earlier versions of this manuscript. Finally, we need to thank and acknowledge the OpenCon community who brought us together, and whose work inspires and invigorates us year after year.
Interactive comment on “Testing the Electrodynamic Method to Derive Height-Integrated Ionospheric Conductances” by

Methodology 1. While the technical approach is largely (see below) well explained the methodology is questionable. When the authors organize their data by IMF, dipole tilt angle, F10.7 and so on the assumption is that these parameters are indeed controlling the ionospheric electrodynamics. There is a causality implied in the approach which opens two fundamental questions: is there a cause-and-effect and if so what is the delay? I think this may work on the dayside where delays between SW conditions and the response of the ionospheric electrodynamics are likely on the order of minutes
Structural style of the Languedoc Pyrenean thrust belt in relation with the inherited Mesozoic structures and with the rifting of the Gulf of Lion margin, southern France

The E-trending Pyrenean orogen results from the inversion of the mid-Cretaceous rift structures responding to an overall N-S extension, as suggested by the balanced and restored cross-sections oriented normal to the orogen. However, oblique convergence/divergence that involve strain partitioning and arcuate segments of the orogenprevent simple tectonic restorations. TheLanguedoc region (southern France) provides a case study of a complex polyphase deformation involving a range of reactivated structures and cross-cutting relationships, acquired in response to varying tectonic stresses with different orientations. We analyze and correlate the onshore-offshore structures of theLanguedoc region, basedon reassessmentof existing andnewly acquired subsurface data. New results in the poorly documented coastal area point to the existence of unrecognized major structures that improves onshore-offshore correlations. Our results show: (i) the part played by the Mesozoic (Early Jurassic, then mid-Cretaceous) extensional phases in the development and the localization of Pyrenean-related contractional structures; (ii) the control of inherited crustal structure on the later Oligocene rifting of the Gulf of Lion. This restoration of the Pyrenean shortening and Oligocene rifting, constructedalongsections (approximatelyperpendicular toeachother) indicatesminimumshorteningof28 km and extension of 14 km, respectively, in the Languedoc foreland. Integration of the Pyrenean structural framework of Languedoc reveals a wide, NE-trending transfer zone linking the eastern Pyrénées to Provence.
Biomechanical Research Project at the VI"' World Championships in Athletics, Athens 1997: Preliminary Report

The International Athletic Foundation appointed the Institute for Athletics of the German Sport University Cologne to carry out a Biomechanical Research Project during the 6"' World Championships in Athletics in Athens 1997, This scientific approach was intended to be a follow-up study to that carried out al the 2"'' World Championships in Rome 1987. which was the first extensive data-capture of elite athletes under competitive conditions in different track and field events.
RISS Discussion Paper Series

In a conventional experimental design for insurance purchase, we incorporate low and high degrees of variances of loss-occurrence probabilities under no-loss and loss treatments and create three treatment groups: NA (a treatment group with known probabilities of an unlucky event occurring), LA, and HA (treatment groups with low/high variances of loss-occurrence probabilities). Then, we conclude that the aversion behaviors in NA and HA are consistent with the existing economic theories such as the ambiguity aversion model and prospect theory; on the contrary, those in LA cannot be solved by them even if we combine them.
REDEFINING THE ROLE OF NATURAL HISTORY COLLECTIONS AND MUSEUMS IN AN ERA OF GLOBAL CLIMATE CHANGE

Natural history collections (NHCs) have accumulated billions of specimens as permanent records of the diversity of the world’s natural heritage. For centuries, biological museums have typically supported the goals of taxonomy, systematics, biogeography and public education. In this time of rapid environmental change, herbarium specimens in NHCs have been employed to provide phenological and distributional data that are indicative of rising temperatures and for tracking alien plant introductions. Historical herbarium materials can also provide long-term proxy datasets useful for reconstructing past ecological conditions and which may also be useful for projecting future trends. Changing times require NHCs to re-define their goals so as to remain relevant and sustainable.
Leptin and Female Reproductive Health

Leptin is a peptide hormone, secreted primarily by the adipose tissue, placenta being the second leptin-producing tissue in humans. Apart from playing an integral role in food intake regulation and energy balance, leptin is an important signalling molecule affecting human reproduction. Accumulated evidence suggests that leptin has potential roles in the regulation of GnRH and LH secretion, puberty, pregnancy, and lactation. Deregulation of leptin levels has been associated with several reproductive disorders including infertility, recurrent pregnancy loss, and polycystic ovary syndrome. This chapter illustrates the importance of leptin in female reproductive health, its role in the metabolic regulation of reproductive axis and its eventual pathophysiological implications in prevalent reproductive disorders.
Evaluation of impregnants designed for all-film power capacitors engineering: Electric conduction and breakdown

An experimental study of conduction and breakdown phenomena of M/DBT (monodibenzyltoulene) being used as polypropylene impregnant in the all-film capacitor technology is reported. The liquid electric losses exhibit a strong interfacial dependence when the liquid is in contact with a metallic or a polymer, (either impregnated or dry) interface. Charge-carrier injection in the neighborhood of the interface is the dominant contribution of high-field liquid conductivity. The breakdown phenomena are shown to be related either to high-field conduction or to the presence of particles or to local field enhancements. The dielectric properties of inhomogeneous media constituted by a glassy semicrystalline polymer (polypropylene) impregnated by M/DBT are explored. The measured permittivity is compared to various forms of mixture equations. The closest agreement is obtained with the Lichteneker's logarithmic mixing expression.
Network interdependence and information dynamics in cyber-physical systems

The cyber-physical systems (CPS) are emerging as the underpinning technology for major industries in the 21th century. This dissertation is focused on two fundamental issues in cyber-physical systems: network interdependence and information dynamics. It consists of the following two main thrusts. The first thrust is targeted at understanding the impact of network interdependence. It is shown that a cyber-physical system built upon multiple interdependent networks are more vulnerable to attacks since node failures in one network may result in failures in the other network, causing a cascade of failures that would potentially lead to the collapse of the entire infrastructure. There is thus a need to develop a new network science for modeling and quantifying cascading failures in multiple interdependent networks, and to develop network management algorithms that improve network robustness and ensure overall network reliability against cascading failures. To enhance the system robustness, a “regular” allocation strategy is proposed that yields better resistance against cascading failures compared to all possible existing strategies. Furthermore, in view of the load redistribution feature in many physical infrastructure networks, e.g., power grids, a CPS model is developed where the threshold model and the giant connected component model are used to capture the node failures in the physical infrastructure network and the cyber network, respectively. The second thrust is centered around the information dynamics in the CPS. One speculation is that the interconnections over multiple networks can facilitate information diffusion since information propagation in one network