Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy.

BACKGROUND Targeting GBM energy metabolism through multiple metabolic pathways has emerged as an effective therapeutic approach. Dual inhibition of phospholipid and mitochondrial metabolism with cytoplasmic phospholipase A2 (cPLA2) knockdown and metformin treatment could be a potential strategy. However, the strategic prerequisite is to explore a carrier capable of co-delivering the therapeutic combination to cross the blood-brain barrier (BBB) and preferentially accumulate at the GBM site. METHODS Blood exosomes (Exos) were selected as the combination delivery carriers. The cellular uptake of Exos and the therapeutic effects of the combination strategy were evaluated in primary GBM cells. In vivo GBM-targeted delivery efficiency and anti-GBM efficacy were tested in a patient-derived xenograft model. RESULTS Here, we showed that the Exos-mediated cPLA2 siRNA/metformin combined strategy could regulate GBM energy metabolism for personalized treatment. Genomic analysis and experiments showed that polymerase 1 and transcript release factor (PTRF, a biomarker of GBM) positively regulated the uptake of Exos by GBM cells, confirming the feasibility of the delivery strategy. Further, Exos could co-load cPLA2 siRNA (sicPLA2) and metformin and co-deliver them across the BBB and into GBM tissue. The mitochondrial energy metabolism of GBM was impaired with this combination treatment (Exos-Met/sicPLA2). In the patient-derived xenograft GBM model, systemic administration of Exos-Met/sicPLA2 reduced tumor growth and prolonged survival. CONCLUSIONS Our findings demonstrated that Exos-based combined delivery of sicPLA2 and metformin selectively targeted the GBM energy metabolism to achieve antitumor effects, showing its potential as a personalized therapy for GBM patients.
Melatonin promotes the development of sheep transgenic cloned embryos by protecting donor and recipient cells

ABSTRACT The yield efficiency of transgenic animal generation is relatively low[1]. To improve its efficiency has become a priority task for researchers[2]. Melatonin (N-acetyl-5-methoxytryptamine, MT) is a potent-free radical scavenger and antioxidant to protect mitochondria, lipids, protein and DNA from oxidative stress[3]. In this study, we observed that improving the quality of both donor and recipient cells by giving physiological concentration (10−7 M) of MT significantly increase the sheep transgenic embryo development in the in vitro condition. MT promotes the donor cell viability, proliferation, efficiency of monoclonal formation and the electrotransferring efficiency of fetal fibroblast cells (FFCs). The mechanistic exploration indicates that MT has the capacity for the synchronization of cell division cycle, reduction of cellular oxidative stress, apoptosis, and the increase of mitochondrial number and function. All of these render MT’s ability to increase the efficiency of animal transgenic processes such as somatic cell nuclear transfer (SCNT) and electroporation. The outcomes are the increased cleavage rate and blastocyst rate of the transgenic sheep embryos after MT treatment. These beneficial effects of MT on transgenic embryo development are worth to be tested in the in vivo condition in the future.
Research on Power Combining with Two Coherent Signals at W Band

In this paper,a new power combiner at W band is proposed,i.e.,the coherent power combiner,in which a injection locked amplifier chain is used as basic amplifier unit and a H-T waveguide junction is used as 3dB power divider and combiner nets.On the other hand,four IMPATT amplifiers with 75mW rating output power are used.The experimental results show that the output power of this new W band coherent power combiner is as high as 250mW at the center frequency 93.23GHz and its operation band width is about 60MHz.Furthermore,the combining efficiency is about 80% and the DC to RF conversion efficiency is about 10%. Finally,the experiment and analysis indicate that coherent power combiner can work efficiently at W band and provide large enough power for the transmitter.
Curative Cell and Gene Therapy for Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) describes a series of genetic bone fragility disorders that can have a substantive impact on patient quality of life. The multidisciplinary approach to management of children and adults with OI primarily involves the administration of antiresorptive medication, allied health (physiotherapy and occupational therapy), and orthopedic surgery. However, advances in gene editing technology and gene therapy vectors bring with them the promise of gene‐targeted interventions to provide an enduring or perhaps permanent cure for OI. This review describes emergent technologies for cell‐ and gene‐targeted therapies, major hurdles to their implementation, and the prospects of their future success with a focus on bone disorders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Machine Learning Predictability of Clinical Next Generation Sequencing for Hematologic Malignancies to Guide High-Value Precision Medicine

Advancing diagnostic testing capabilities such as clinical next generation sequencing methods offer the potential to diagnose, risk stratify, and guide specialized treatment, but must be balanced against the escalating costs of healthcare to identify patient cases most likely to benefit from them. Heme-STAMP (Stanford Actionable Mutation Panel for Hematopoietic and Lymphoid Malignancies) is one such next generation sequencing test. Our objective is to assess how well Heme-STAMP pathological variants can be predicted given electronic health records data available at the time of test ordering. The model demonstrated AUROC 0.74 (95% CI: [0.72, 0.76]) with 99% negative predictive value at 6% specificity. A benchmark for comparison is the prevalence of positive results in the dataset at 58.7%. Identifying patients with very low or very high predicted probabilities of finding actionable mutations (positive result) could guide more precise high-value selection of patient cases to test.
Focal Serous Tubal Intra-Epithelial Carcinoma Lesions Are Associated With Global Changes in the Fallopian Tube Epithelia and Stroma

Objective Serous tubal intra-epithelial carcinoma (STIC) lesions are thought to be precursors to high-grade serous ovarian cancer (HGSOC), but HGSOC is not always accompanied by STIC. Our study was designed to determine if there are global visual and subvisual microenvironmental differences between fallopian tubes with and without STIC lesions. Methods Computational image analyses were used to identify potential morphometric and topologic differences in stromal and epithelial cells in samples from three age-matched groups of fallopian tubes. The Benign group comprised normal fallopian tubes from women with benign conditions while the STIC and NoSTIC groups consisted of fallopian tubes from women with HGSOC, with and without STIC lesions, respectively. For the morphometric feature extraction and analysis of the stromal architecture, the image tiles in the STIC group were further divided into the stroma away from the STIC (AwaySTIC) and the stroma near the STIC (NearSTIC). QuPath software was used to identify and quantitate secretory and ciliated epithelial cells. A secretory cell expansion (SCE) or a ciliated cell expansion (CCE) was defined as a monolayered contiguous run of >10 secretory or ciliated cells uninterrupted by the other cell type. Results Image analyses of the tubal stroma revealed gradual architectural differences from the Benign to NoSTIC to AwaySTIC to NearSTIC groups. In the epithelial topology analysis, the relative number of SCE and the average number of cells within SCE were higher in the STIC group than in the Benign and NoSTIC groups. In addition, aging was associated with an increased relative number of SCE and a decreased relative number of CCE. ROC analysis determined that an average of 15 cells within SCE was the optimal cutoff value indicating the presence of a STIC lesion in the tubal epithelium. Conclusions Our findings suggest that global stromal alterations and age-associated reorganization of tubal secretory and ciliated cells are associated with STIC lesions. Further studies will need to determine if these alterations precede STIC lesions and provide permissible conditions for the formation of STIC.
Potential Therapeutic Targets of Rehmannia Formulations on Diabetic Nephropathy: A Comparative Network Pharmacology Analysis

Background: Previous retrospective cohorts showed that Rehmannia-6 (R-6, Liu-wei-di-huang-wan) formulations were associated with significant kidney function preservation and mortality reduction among chronic kidney disease patients with diabetes. This study aimed to investigate the potential mechanism of action of common R-6 variations in a clinical protocol for diabetic nephropathy (DN) from a system pharmacology approach. Study Design and Methods: Disease-related genes were retrieved from GeneCards and OMIM by searching “Diabetic Nephropathy” and “Macroalbuminuria”. Variations of R-6 were identified from a published existing clinical practice guideline developed from expert consensus and pilot clinical service program. The chemical compound IDs of each herb were retrieved from TCM-Mesh and PubChem. Drug targets were subsequently revealed via PharmaMapper and UniProtKB. The disease gene interactions were assessed through STRING, and disease–drug protein–protein interaction network was integrated and visualized by Cytoscape. Clusters of disease–drug protein–protein interaction were constructed by Molecular Complex Detection (MCODE) extension. Functional annotation of clusters was analyzed by DAVID and KEGG pathway enrichment. Differences among variations of R-6 were compared. Binding was verified by molecular docking with AutoDock. Results: Three hundred fifty-eight genes related to DN were identified, forming 11 clusters which corresponded to complement and coagulation cascades and signaling pathways of adipocytokine, TNF, HIF-1, and AMPK. Five variations of R-6 were analyzed. Common putative targets of the R-6 variations on DN included ACE, APOE, CCL2, CRP, EDN1, FN1, HGF, ICAM1, IL10, IL1B, IL6, INS, LEP, MMP9, PTGS2, SERPINE1, and TNF, which are related to regulation of nitric oxide biosynthesis, lipid storage, cellular response to lipopolysaccharide, inflammatory response, NF-kappa B transcription factor activity, smooth muscle cell proliferation, blood pressure, cellular response to interleukin-1, angiogenesis, cell proliferation, peptidyl-tyrosine phosphorylation, and protein kinase B signaling. TNF was identified as the seed for the most significant cluster of all R-6 variations. Targets specific to each formulation were identified. The key chemical compounds of R-6 have good binding ability to the putative protein targets. Conclusion: The mechanism of action of R-6 on DN is mostly related to the TNF signaling pathway as a core mechanism, involving amelioration of angiogenesis, fibrosis, inflammation, disease susceptibility, and oxidative stress. The putative targets identified could be validated through clinical trials.
Quality of Life of Post-stroke Patients

Abstract Introduction Stroke is a disease whose consequences have a considerable impact on the quality of the patient’s life. It is a widespread disease that has a disabling impact on life and, in addition to physical changes, brings about a number of psychological and cognitive processes. Goal The goal of the study was to identify and describe the quality of life of post-stroke patients. Methodology The study design was quantitative. A questionnaire of the authors’ own design and the SF-36 questionnaire were used to obtain the data. Results Significant differences in patient quality of life were identified in relation to patient gender. Moreover, the quality of life in all individual SF-36 dimensions, except for mental health, deteriorated with age. With regard to occupational placement, employed respondents gave the highest evaluation of quality of life according to SF-36 and old-age pensioners the lowest. The analysis shows that quality of life in individual dimensions is positively influenced by respondents’ higher education. The evaluation in individual dimensions improves with the time that has passed since the stroke. Conclusion The quality of life of post-stroke patients deteriorates with age. The deteriorating level of patient quality of life in older age requires programmes that include assessments and interventions that lead to the treatment of these patients.
Genetic characterisation of centuries-old oak and linden trees using SSR markers

Abstract The main goal of this study was to identify the unique gene pool of old and historically valuable Quercus robur L. and Tilia cordata L. to be able to characterise their genetic diversity in order to determine the polymorphism by expressed sequence tag-single sequence repeat (EST-SSR) markers and identify the most valuable specimens. Morphological description, molecular genetic analysis, and statistical analysis were used in studies. The genetic distances between old-value trees of different Quercus L. and Tilia L. were determined based on EST-SSR markers and morphological characteristics. Using polymerase chain reaction (PCR), alleles of the expected size were obtained. It was determined that four to eight alleles were obtained by seven SSR markers in the studied Q. robur L. samples. According to the calculated value of the locus polymorphism index (polymorphism information content [PIC]), the most polymorphic was the marker SSRQrZAG 65; the PIC was 0.84. The lowest value of PIC was observed in the marker SSRQrZAG 11; the PIC was 0.69. Intragenetic polymorphism was detected for all studied markers. Among the studied samples of linden, two to five alleles were identified. It was found that the highest value of PIC was obtained for the marker Ts920 – 0.72. The least polymorphic was the marker Ts927 (PIC was 0.28), which is not only due to the small number of alleles, but also their uneven distribution in the sample. Intragenetic polymorphism was detected in four of the six markers analysed for T. cordata L. In this study, polymorphism was detected in all studied samples of Q. robur L. and T. cordata L. , which allows to assess their genetic diversity based on the distribution of alleles.
Challenges in Discovering Patient Journey Processes

Research in the area of process analytics has become useful in providing new insights into patient care and support decision making. In order to reach the full potential of process analytics, we must look into further details and address challenges when applying it to real world scenarios which are often represented by complex systems. One area that has not been explored thoroughly is the ability to identify how processes relate to each other in a network of processes. Different often overlapping information about someone or something will always be kept in different domains. There is rarely a chance for these pieces of information to all link together and access them directly. Having access to the relation between processes and seeing an overall picture of network of process helps to better understanding a complex system and further analyse it to make better and informed decisions. However, attempts to link these processes into a network has led to challenges which have not been resolved yet. The contribution is a detailed use case that highlights existing challenges in discovering patient journey processes and two experimentation with preliminary results on addressing some of the identified challenges. The first experiment investigated compliance checking of clinical processes against guidelines and the second investigated the matching of event labels with an existing processable collection of health terms. The results of both experiments showed that further research and tool development is required to increase the automation for compliance checking and improve the accuracy of event and term matching.
Revisiting Social Media in Health Care: A Bakhtinian Carnival Perspective

Understanding the value of social media in health care has been a conundrum. Much of the literature in this area focuses on the use of social media for promotion, with very few studies seeking to elucidate how social media yields value in health care settings. This article draws on concepts from 18th century linguist Mikhail Bahktin to explain that social media acts like a Carnival in suspension of behavioral norms, and the provision of a forum for the proliferation of diverse dialogues. As a Carnival, social media plays an important role in encouraging dialogues that would not be appropriate within other spaces in the health care system. As such, social media is playing a pivotal role in changing norms toward shared care and patient empowerment.
“Rather Solve the Problem from Scratch”: Gamesploring Human-Machine Collaboration for Optimizing the Debris Collection Problem

Optimizing operations on critical infrastructure networks is key to reducing the impact of disruptive events. In this paper, we explore the potential of having humans and algorithms work together to address this difficult task. For this purpose, we use a gamified experiment to build and assess this potential in the context of the debris collection problem (i.e., “gamesploring”). We developed a digital game where players can request the help of the computer while facing a multi-objective problem of assigning contractors to road segments for clearing debris in a disaster area. Through a within-subjects experimental study, we assessed how players optimized under various circumstances (e.g., initial solution vs. from scratch) compared to the computer on its own. The results are both surprising as well as insightful: they suggest that human-machine collaboration is indeed beneficial but also that more work is needed on how to appropriately guide this form of collaboration.
Addressing Accessibility Barriers in Programming for People with Visual Impairments: A Literature Review

Accessibility issues with programming languages and programming environments pose a major barrier for students with visual impairments to participate in computing related courses as well as threatens the productivity of professional programmers with visual impairments. To remedy this, the past two decades have witnessed an increase in accessibility research designed to investigate and address the challenges faced by people with visual impairments while programming or learning how to program. We conducted a literature review of accessibility research in this domain. The aim was to identify, aggregate, and highlight known accessibility barriers to programming faced by professional programmers and students with visual impairments learning how to code as well as to identify all solutions that have been proposed to address these barriers. We selected and analyzed 70 papers reporting on accessibility of programming and programming environments for people with visual impairments. Numerous barriers to programming by people with visual impairments have been identified in the literature. Some of these barriers are understudied and present opportunities for future work. A lot of studies have also proposed tools and new accessible programming languages to address the accessibility issues of current programming languages and programming environments.
Explaining Recommendations in E-Learning: Effects on Adolescents' Trust

In the scope of explainable artificial intelligence, explanation techniques are heavily studied to increase trust in recommender systems. However, studies on explaining recommendations typically target adults in e-commerce or media contexts; e-learning has received less research attention. To address these limits, we investigated how explanations affect adolescents’ initial trust in an e-learning platform that recommends mathematics exercises with collaborative filtering. In a randomized controlled experiment with 37 adolescents, we compared real explanations with placebo and no explanations. Our results show that real explanations significantly increased initial trust when trust was measured as a multidimensional construct of competence, benevolence, integrity, intention to return, and perceived transparency. Yet, this result did not hold when trust was measured one-dimensionally. Furthermore, not all adolescents attached equal importance to explanations and trust scores were high overall. These findings underline the need to tailor explanations and suggest that dynamically learned factors may be more important than explanations for building initial trust. To conclude, we thus reflect upon the need for explanations and recommendations in e-learning in low-stakes and high-stakes situations.
Colorbo: Envisioned Mandala Coloringthrough Human-AI Collaboration

Mandala coloring is popular among many people, from children to adults, and many studies have revealed its benefits in mental well-being. However, our preliminary study results reveal difficulties in mandala coloring tasks, such as selecting harmonious colors/areas and envisioning how each selection affects the final output. This paper presents Colorbo, an interactive system based on human-AI collaboration to envision mandala coloring. Colorbo and its user colorize a mandala individually by watching each other work. The user shows a colored mandala in progress, and Colorbo fills in the remaining areas by analyzing the patterns and color combinations of the user’s image. Colorbo then projects the complete mandala onto the paper the user is colorizing, and the user continues coloring by envisioning the outcome based on images from Colorbo. We conducted a within-subject study to investigate the effectiveness of Colorbo. Our quantitative and qualitative analysis results show the positive experiences of the participants, concerns regarding the coloring behavior with Colorbo, and their preferred projection method for envisioning a mandala. Finally, based on the findings, we discuss the design implications for human-AI collaboration in the area of art.
Analyses on Multi-sensor Fingerprint Enhancement and Indexing

Fingerprint biometric has been widely applied in both forensic law enforcement and security applications, and the most common application is access control. In recent years, we have witnessed the development of touchless fingerprint acquisition technology, which can generate 3D representation of fingerprints. Although some research has been carried out on 3D fingerprint feature extraction (e.g. 3D minutiae) and identification, it is computationally expensive and time-consuming to compare two sets of 3D minutiae in real time. Therefore, the common way to develop an Automatic Fingerprint Identification System (AFIS) using 3D fingerprints is to unwrap 3D fingerprints into 2D equivalent images, then the existing algorithms for 2D fingerprint processing can be utilized. In this paper, we present some observations of 2D to 3D (unraveled 2D equivalent images from 3D model) fingerprints recognition based on a publicly available database. We tested the performance of 2D to 3D fingerprint verification using enhanced unraveled 2D equivalent images. The results show that the cropped enhanced 3D images based on singular points can achieve the best performance. Since enhanced fingerprint images can result in efficient fingerprint indexing, we also made some analyses on the hash bit selection of MCC indexing scheme using the cropped enhanced 3D images based on singular points.