Miracle-dz/UniFAR-FTUs huggingface dataset:
An Injectable Platform of Engineered Cartilage Gel and Gelatin Methacrylate to Promote Cartilage Regeneration

Cell–hydrogel constructs are frequently used as injectable platforms for irregular cartilage regeneration. However, cell–hydrogel constructs have obvious disadvantages, such as long culture times, high probability of infection, and poor cartilage formation capacity, significantly limiting their clinical translation. In this study, we aimed to develop a novel injectable platform comprising engineered cartilage gel (ECG) and gelatin methacrylate (GelMA) to improve cartilage regeneration. We first prepared an ECG by cutting the in vitro engineered cartilage sheet into pieces. The chondrocytes and ECG were evenly encapsulated into GelMA to form Cell-GelMA and ECG-GelMA constructs. The ECG-GelMA construct exhibited preferred gel characteristics and superior biocompatibility compared with the Cell-GelMA construct counterpart. After subcutaneous implantation in nude mice and goat, both gross views and histological evaluations showed that the ECG-GelMA construct achieved more homogenous, stable, and mature cartilage regeneration than the Cell-GelMA construct. Immunological evaluations showed that ECG-GelMA had a mitigatory immunologic reaction than the Cell-GelMA construct. Overall, the results suggest that the ECG-GelMA is a promising injectable platform for cartilage regeneration that may advance clinical translation.
Adiposity-Related Predictors of Vascular Aging From a Life Course Perspective–Findings From the Helsinki Birth Cohort Study

The main objective of this study was to study predictors of vascular health with focus on adiposity-related factors. Glucose metabolism, blood lipids, inflammatory markers and body composition were assessed 15 years before assessment of vascular health which was assessed with pulse wave velocity (PWV) in 660 subjects born 1934–44. In a univariate analysis in women the strongest association with PWV was seen for age, systolic blood pressure, dysglycemia, dyslipidemia, inflammatory markers and body fat percentage measured in late midlife and PWV measured 15 years later. In men age, body mass index (BMI), systolic blood pressure, dysglycemia, and body fat percentage in late midlife were associated with PWV. One novel finding was that adiposity-related factors were strong predictors of vascular health, something not fully encapsulated in BMI, lean body mass or body fat percentage alone. A higher fat mass index was associated with worse vascular health, which was not ameliorated by a higher lean mass index. Our findings stress the importance to study body composition and fat and lean body mass simultaneously because of their close interaction with each other also in relation to vascular health.
The Efficacy and Safety of Bivalirudin Versus Heparin in the Anticoagulation Therapy of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis

Background: Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown. Methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin’s efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performed via the RevMan version 5.3. 5 Software and STATA version 15.1 Software. Results: Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I 2 = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04–0.66), patient thrombosis (I 2 = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37–0.93), in-circuit thrombosis/interventions (I 2 = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24–0.68), and in-hospital mortality (I 2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46–0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I 2 = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46–1.62), 30-day mortality (I 2 = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41–1.68), and ECMO duration in adults (I 2 = 41%, p = 0.75, mean difference (MD) = −3.19, 95% CI: −23.01–16.63) and children (I 2 = 76%, p = 0.65, MD = 40.33, 95% CI:−135.45–216.12). Conclusions: Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.
Contextualization of Religion and Entrepreneurial Performance: A Lens of Buddhist Small Business Entrepreneurs

This study explores the manifestation of Buddhism's conception in underlying entrepreneurial performance. The study is a qualitative research approach with a development direction that comes from successful Buddhist small business entrepreneurs in Bekasi, Indonesia. The interpretive paradigm is used to interpret social life in the reality of successful Buddhist small business entrepreneurs on entrepreneurial performance. Data collection using in-depth interviews with Buddhist small business entrepreneurs in an open-ended format. Data analysis was done in many stages, including domain analysis, taxonomy analysis, component analysis, and theme analysis. The findings indicate that religion acts as an institution that legitimizes the formation of entrepreneurial performance. The performance of Buddhist small business entrepreneurs is manifest in their management of economic or material achievements, and their religious observance in a broad socio-economic context in the relationship of three aspects of human life, namely the individual, social, and environmental, as a form of entrepreneurial practice based on Buddhist values. This research reveals the embodiment of social responsibility for small business Buddhist entrepreneurs which is reflected in entrepreneurial performance through the manifestation of religious values. The findings provide theoretical relevance in institutional theory.
Assessment of the Transmission Dynamics of Clostridioides difficile in a Farm Environment Reveals the Presence of a New Toxigenic Strain Connected to Swine Production

The recent increase in community-acquired Clostridioides difficile infections discloses the shift in this bacterium epidemiology. This study aimed at establishing a transmission network involving One Health components, as well as assessing the zoonotic potential and genomic features of dominant clones. Samples were collected from different compartments of animal, human and environmental origin, from an animal production unit. C. difficile isolates were characterized for toxigenic profile by multiplex-PCR, while genetic diversity was evaluated by PCR-ribotyping and whole genome-based analysis. The overall C. difficile prevalence was 37.2% (70/188), and included samples from environmental (58.3%, 35/60) and animal (31.5%, 35/111) compartments; human samples (n = 17) taken from healthy workers were negative. A predominant clone from RT033 was found in almost 90% of the positive samples, including samples from all compartments connected to the pig production unit, with core-genome single nucleotide variant (SNV)-based Analysis supporting a clonal transmission between them (mean distance of 0.1 ± 0.1 core-SNVs). The isolates from this clone (herein designated PT RT033) were positive for all C. difficile toxin genes (tcdA, tcdB, cdtA/cdtB). The phyloGenetic positioning of this clone was clearly distinct from the classical RT033 cluster, suggesting a different evolutionary route. This new clone shares genomic features with several RTs from the clade 5 Sequence Type (ST) 11, including a complete pathogenicity locus (PaLoc) that is more similar to the one found in toxigenic strains and contrasting to the less virulent classical RT033 (tcdA-, tcdB-, cdtA + /cdtB +). The presence of a tcdA gene truncated into two ORFs, not previously described, requires further evaluation concerning toxin functionality. We hypothesize that the unique combination of genetic elements found in the PT RT033 clone may contribute to host tropism and environmental dissemination and maintenance. This study constitutes the first report of a toxigenic RT033 clone and adds to the overall knowledge on Clade 5 sequence type 11, considered the C. difficile evolutionary lineage with the highest zoonotic potential. The presence of this clone in all compartments associated with the pig production unit suggests a transmission chain involving these animals and contributes to unveil the role played by animal and environmental reservoirs in this pathogen epidemiology.
Finding Our Bearings in Post-method Waters

This paper proposes a framework to guide us in designing and implementing our classroom language pedagogy. It is based on three major principles which the teacher can keep constantly in mind: that the learners need to be engaged, that the language needs to be memorized, and that learning needs to move toward communicative competence. Each principle generates between two and four dimensions which the teacher can use to develop specific strategies.
The Social Science of Institutional Transformation: Intersectional Change in the Academy

This article examines intersectional praxis as an approach to institutional transformation, arguing that intersectionality is both a catalyst for and outcome of gender equity efforts in the social sciences and other academic STEM fields. As such, approaching gender equity intersectionally can be understood as a way that theory and practice are co-constitutive in social science and hence an important aspect of transforming academic institutions. Through a case study of the US National Science Foundation (NSF) ADVANCE program for gender equity in STEM, I look at the development of ADVANCE from an effort to support women in scientific fields to becoming a program for institutional transformation grounded in an intersectional understanding of women's inequity in the academic labor force. I ask two related questions in the efforts to address gender inequities in STEM. First, what is the relationship between academic institutions (which are simultaneously sites for the discovery of knowledge and gender inequality) and the National Science foundation, as the premier American academic institutional funding agency? Second, how has this relationship, through those working on ADVANCE, fundamentally shifted the understanding of the social scientific tools and strategies necessary to advance equity for women in academia? In looking at these questions, I argue that, beyond women's representation in social sciences and academia broadly, intersectionality is an important scholarly advance in social science that offers a dialectical tool for change.
High-Throughput Native Mass Spectrometry Screening in Drug Discovery

The design of new therapeutic molecules can be significantly informed by studying protein-ligand interactions using biophysical approaches directly after purification of the protein-ligand complex. Well-established techniques utilized in drug discovery include isothermal titration calorimetry, surface plasmon resonance, nuclear magnetic resonance spectroscopy, and structure-based drug discovery which mainly rely on protein crystallography and, more recently, cryo-electron microscopy. Protein-ligand complexes are dynamic, heterogeneous, and challenging systems that are best studied with several complementary techniques. Native mass spectrometry (MS) is a versatile method used to study proteins and their non-covalently driven assemblies in a native-like folded state, providing information on binding thermodynamics and stoichiometry as well as insights on ternary and quaternary protein structure. Here, we discuss the basic principles of native mass spectrometry, the field’s recent progress, how native MS is integrated into a drug discovery pipeline, and its future developments in drug discovery.
Germline Mutational Landscape in Chinese Patients With Advanced Breast Cancer

Background Genetic testing for breast cancer (BC) patients may shift the paradigm towards more personalized management and treatment strategies. While gene alterations may be ethnic-specific in breast cancer, our understanding of genetic epidemiology of BC remains mainly driven by data from Caucasian populations and further limited to selected handful of genes. Methods We collected whole blood samples from 356 BC patients at metastatic first line BC and primary stage IV disease at Beijing Cancer Hospital between Jan. 2013 to Dec. 2019. A comprehensive 600-gene cancer panel was used to detect germline variants in the covered genes with a median 300x sequencing depth. Variants were classified into pathogenic, likely pathogenic, variant of uncertain significance, likely benign and benign groups according to the ACMG/AMP Standards and Guidelines. Pathogenic and likely pathogenic variants were considered as deleterious mutations. Results The median age of 356 BC patients was 49 years (range, 21-87 years) at the first diagnosis of BC. Deleterious germline mutations across 48 cancer-related genes were identified in 21.6% (77/356) of the patients. The most prevalent mutations were BRCA1/2 mutations (7.0%), followed by ATM and RAD50 mutations (1.4% each). In addition, patients with family history were more likely to carry BRCA1 mutations (P=0.04). Moreover, patients with triple-negative breast cancer (TNBC) were more likely to harbor BRCA1 mutations than those with HR+ or HER2+ breast cancer (P=0.006). While there was no significant survival difference observed in BRCA1/2 carriers relative to non-carriers, patients with DNA damage repair (DDR) gene mutations (mostly frequently BRCA, ATM, RAD50) had worse disease-free survival (P=0.02). Conclusions The most prevalent germline mutations in a large cohort of Chinese patients with advanced BC were BRCA1/2 mutations, followed by ATM and RAD50 mutations. In total, approximately 16.0% (57/356) of patients carry deleterious mutations in DDR pathway. Patients with breast or ovarian cancer family history were more likely to carry BRCA1/2 mutations, and ones with DDR mutations had worse survival. These findings suggest that DDR mutations are prevalent in Chinese BC patients who may potentially benefit from treatment with Poly (ADP-ribose) polymerase inhibitors.
Image Analysis of the Mitochondrial Network Morphology With Applications in Cancer Research

Mitochondria are dynamic organelles that integrate bioenergetics, biosynthesis, and signaling in cells and regulate redox homeostasis, apoptotic pathways, and cell proliferation and differentiation. Depending on the environmental conditions, the mitochondrial morphology dynamically changes to match the energy demands. The mitochondrial dynamics is related to the initiation, migration, and invasion of diverse human cancers and thus affects cancer metastasis, metabolism, drug resistance, and cancer stem cell survival. We reviewed the current image-based analytical tools and machine-learning techniques for phenotyping mitochondrial morphology in different cancer cell lines from confocal microscopy images. We listed and applied pipelines and packages available in ImageJ/Fiji, CellProfiler, MATLAB, Java, and Python for the analysis of fluorescently labeled mitochondria in microscopy images and compared their performance, usability and applications. Furthermore, we discussed the potential of automatic mitochondrial segmentation, classification and prediction of mitochondrial abnormalities using machine learning techniques. Quantification of the mitochondrial morphology provides potential indicators for identifying metabolic changes and drug responses in cancer cells.
Therapists’ Views of Mechanisms of Change in Psychotherapy: A Mixed-Method Approach

The question of what works in psychotherapy has been a subject of debate in the recent years, occupying both clinicians and researchers. In this study, we aimed to assess the current perspectives held by clinicians regarding the processes which produce changes in psychotherapy, as well as the predictors of specific views. Licensed therapists (n = 107), consisting mainly of psychodynamically and integratively oriented psychologists, were asked to write in their own words what they think works in psychotherapy. Thematic analysis was employed to assess the main mechanisms of change as perceived by the therapists. Differences in the prevalence of specific themes were assessed using Friedman and Wilcoxon signed-rank tests. Univariate logistic regressions were employed to assess the factors that predict the probability of reporting a specific mechanism of change. The results indicated that the therapeutic bond was the most highly reported mechanism of change, followed by theory-driven mechanisms of change, therapist characteristics, therapist professionalism, and client motivation. Male therapists were more likely to indicate the professionalism as a mechanism of change compared to female therapists. Higher education was associated with lower reports of therapists’ characteristics as the mechanisms of change. These results suggest that therapists acknowledge the importance of the working alliance, and that the perception of the mechanism of change is associated with various factors which comprise therapist orientation. Limitations and directions for future research are discussed.
Non-Mycorrhizal Fungal Presence Within Roots Increases Across an Urban Gradient in Berlin, Germany

Symbioses between plants and fungi are important in both promoting plant fitness and maintaining soil structure. The ways in which these relationships change across an urban gradient is subject to debate. Here we measured root colonisation including the presence of arbuscular mycorrhizal fungi, non-mycorrhizal fungi, and root hair presence. We found no evidence of changes in levels of arbuscular mycorrhizal fungal colonisation across an urban gradient, colonisation levels being driven instead by plant community. However, we did observe an increase in non-mycorrhizal fungal colonisation in association with increasing urbanity. Additionally, we observed an urban-related increase in root hair presence. Using principal component analysis we were able to provide strong evidence for these patterns being driven by an “urban syndrome”, rather than soil chemistry. Our findings have important implications for the wider understanding of abiotic stresses on fungal endophyte presence and shed light on the impacts of urbanity upon plant roots.
Molecular Approaches for the Validation of the Baboon as a Nonhuman Primate Model for the Study of Zika Virus Infection

Nonhuman primates (NHP) are particularly important for modeling infections with viruses that do not naturally replicate in rodent cells. Zika virus (ZIKV) has been responsible for sporadic epidemics, but in 2015 a disseminated outbreak of ZIKV resulted in the World Health Organization declaring it a global health emergency. Since the advent of this last epidemic, several NHP species, including the baboon, have been utilized for modeling and understanding the complications of ZIKV infection in humans; several health issues related to the outcome of infection have not been resolved yet and require further investigation. This study was designed to validate, in baboons, the molecular signatures that have previously been identified in ZIKV-infected humans and macaque models. We performed a comprehensive molecular analysis of baboons during acute ZIKV infection, including flow cytometry, cytokine, immunological, and transcriptomic analyses. We show here that, similar to most human cases, ZIKV infection of male baboons tends to be subclinical, but is associated with a rapid and transient antiviral interferon-based response signature that induces a detectable humoral and cell-mediated immune response. This immunity against the virus protects animals from challenge with a divergent ZIKV strain, as evidenced by undetectable viremia but clear anamnestic responses. These results provide additional support for the use of baboons as an alternative animal model to macaques and validate omic techniques that could help identify the molecular basis of complications associated with ZIKV infections in humans.
Investigating the Pore Structure Characteristics and Reservoir Capacities of Lower Jurassic Continental Shale Reservoirs in the Northeastern Sichuan Basin, China

The Lower Jurassic shale in the northeastern Sichuan Basin is one of the main research intervals of continental shale gas. The shale pore structure is an important indicator for evaluating the reservoir capacities of shale reservoirs. We concentrate on the pore structure to indicate reservoir capacity using several testing methods, for example, N2 adsorption-high-pressure mercury pore size combined experiments, X-ray diffraction (XRD) experiments, and the total organic carbon (TOC) method. The results show that the clay mineral content of the continental shale is high. The pore type is mainly a mineral matrix pore, followed by an organic matter pore, and the microcracks are locally developed; the distribution interval of the main pore size is mesoporous, between 10 and 50 nm; the pore volumes and specific surface areas of the continental shale reservoirs are negatively correlated or unrelated to the TOC, mainly due to the failure of pore development in the organic vitrinite and fusinite and the occupation of pore volume and adsorption sites by the soluble organic matter. The larger pores are mainly formed by clay minerals; the reservoir capacities of the continental shale reservoirs were evaluated using a two-factor evaluation method of the pore volume and specific surface area. It was found that the continental shale mainly comprises free reservoirs and has a storage gas capability level of II–IV. The research results elucidate the pore structure characteristics and reservoir capacities of the continental shale reservoirs in the northeastern Sichuan Basin, having important theoretical and guiding significance for the gas-bearing evaluation and dessert target optimization of the continental shale in the study area.