Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic potentials of cell death inhibitors in rats with cardiac ischaemia/reperfusion injury

Growing evidence demonstrated that cell death pathways including ferroptosis, apoptosis and necroptosis contribute to cardiac ischaemia/reperfusion (I/R) injury. We hypothesized that ferroptosis, apoptosis and necroptosis contribute differently to myocardial damage during acute cardiac I/R injury. Rats underwent cardiac I/R or sham operation. I/R‐operated rats were divided into 4 groups: vehicle, apoptosis (Z‐vad), ferroptosis (Fer‐1) and necroptosis (Nec‐1) inhibition. Rats in each cell death inhibitor group were subdivided into 3 different dose regimens: low, medium and high. Infarct size, left ventricular (LV) function, arrhythmias and molecular mechanism were investigated. Cardiac I/R caused myocardial infarction, LV dysfunction, arrhythmias, mitochondrial dysfunction, mitochondrial dynamic imbalance, inflammation, apoptosis and ferroptosis. Infarct size, LV dysfunction, mitochondrial dysfunction, apoptosis and ferroptosis were all reduced to a similar extent in rats treated with Z‐vad (low and medium doses) or Fer‐1 (medium and high doses). Fer‐1 treatment also reduced mitochondrial dynamic imbalance and inflammation. No evidence of necroptosis was found in association with acute I/R injury, therefore Nec‐1 treatment could not be assessed. Apoptosis and ferroptosis, not necroptosis, contributed to myocardial damage in acute I/R injury. Inhibitors of these 2 pathways provided effective cardioprotection in rats with I/R injury though modulation of mitochondrial function and attenuated apoptosis and ferroptosis.
Altered Expression of the Hedgehog Pathway Proteins BMP2, BMP4, SHH, and IHH Involved in Knee Cartilage Damage of Patients With Osteoarthritis and Kashin-Beck Disease

Objective To investigate the expression of Hedgehog (HH) signaling pathway proteins in knee articular cartilage from Kashin-Beck disease (KBD) and osteoarthritis (OA) patients. Methods Knee articular cartilage samples were collected from normal (N), OA, and KBD adults (aged 38-60 years) and divided into 3 groups with 6 subjects in each group. The localization of the HH pathway proteins bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 4 (BMP4), Sonic hedgehog (SHH), and Indian hedgehog (IHH) was observed with the microscope after immunohistochemical (IHC) staining. Positive staining cell rates of each proteins were compared. Results The strongest stainings of all proteins were observed in the middle zones of all 3 groups. The positive staining rates of BMP4 and IHH were significantly lower in the OA and KBD groups than those in the N group in all 3 zones. The positive staining rates of BMP2 and SHH tend to be lower in the OA and KBD groups than those in the N group in the deep zone, while higher in the OA and KBD groups than those in the N group in superficial and middle zones. Conclusions Altered expression of the HH pathway proteins BMP2, BMP4, SHH, and IHH was found in OA and KBD articular cartilage. There seemed to be a compensatory effect between SHH and IHH in cartilage damage. Further studies on the pathogenesis of OA and KBD may be carried out from these aspects in the future.
Combined inhibition of IL-6 and IL-8 pathways suppresses ovarian cancer cell viability and migration and tumor growth

Ovarian cancer is the most lethal gynecological cancer type in the United States. The success of current chemotherapies is limited by chemoresistance and side effects. Targeted therapy is a promising future direction for cancer therapy. In the present study, the efficacy of co-targeting IL-6 and IL-8 in human ovarian cancer cells by bazedoxifene (Baze) + SCH527123 (SCH) treatment was examined. ELISA, cell viability, cell proliferation, cell migration, cell invasion, western blotting and peritoneal ovarian tumor mouse model analyses were performed to analyze the expression levels of IL-6 and IL-8, tumor growth, tumor migration and invasion, and the possible pathways of human ovarian cancer cell lines (SKOV3, CAOV3 and OVCAR3) and patient-derived OV75 ovarian cancer cells. Each cell line was treated by monotherapy or combination therapy. The results demonstrated that IL-6 and IL-8 were secreted by human ovarian cancer cell lines. Compared with the DMSO control, the combination of IL-6/glycoprotein 130 inhibitor Baze and IL-8 inhibitor SCH synergistically inhibited cell viability in ovarian cancer cells. Baze + SCH also inhibited cell migration and invasion, suppressed ovarian tumor growth and inhibited STAT3 and AKT phosphorylation, as well as survivin expression. Therefore, co-targeting the IL-6 and IL-8 signaling pathways may be an effective approach for ovarian cancer treatment.
EDNC: Ensemble Deep Neural Network for COVID-19 Recognition

The automatic recognition of COVID-19 diseases is critical in the present pandemic since it relieves healthcare staff of the burden of screening for infection with COVID-19. Previous studies have proven that deep learning algorithms can be utilized to aid in the diagnosis of patients with potential COVID-19 infection. However, the accuracy of current COVID-19 recognition models is relatively low. Motivated by this fact, we propose three deep learning architectures, F-EDNC, FC-EDNC, and O-EDNC, to quickly and accurately detect COVID-19 infections from chest computed tomography (CT) images. Sixteen deep learning neural networks have been modified and trained to recognize COVID-19 patients using transfer learning and 2458 CT chest images. The proposed EDNC has then been developed using three of sixteen modified pre-trained models to improve the performance of COVID-19 recognition. The results suggested that the F-EDNC method significantly enhanced the recognition of COVID-19 infections with 97.75% accuracy, followed by FC-EDNC and O-EDNC (97.55% and 96.12%, respectively), which is superior to most of the current COVID-19 recognition models. Furthermore, a localhost web application has been built that enables users to easily upload their chest CT scans and obtain their COVID-19 results automatically. This accurate, fast, and automatic COVID-19 recognition system will relieve the stress of medical professionals for screening COVID-19 infections.
Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells

DNA methylation, repressive histone modifications, and PIWI-interacting RNAs are essential for controlling retroelement silencing in mammalian germ lines. Dysregulation of retroelement silencing is associated with male sterility. Although retroelement silencing mechanisms have been extensively studied in mouse germ cells, little progress has been made in humans. Here, we show that the Krüppel-associated box domain zinc finger proteins are associated with DNA methylation of retroelements in human primordial germ cells. Further, we show that the hominoid-specific retroelement SINE-VNTR-Alus (SVA) is subjected to transcription-directed de novo DNA methylation during human spermatogenesis. The degree of de novo DNA methylation in SVAs varies among human individuals, which confers significant inter-individual epigenetic variation in sperm. Collectively, our results highlight potential molecular mechanisms for the regulation of retroelements in human male germ cells.
Low dietary diversity is associated with linear growth faltering and subsequent adverse child developmental outcomes in rural Democratic Republic of the Congo (REDUCE program)

Abstract The objective of this study was to investigate the association between dietary diversity, child growth and child developmental outcomes. This was a prospective cohort study. Developmental outcomes were assessed by communication, fine motor, gross motor, personal social, problem solving and combined developmental scores measured by the Extended Ages and Stages Questionnaire (EASQ) at a 6‐month follow‐up visit. Height and weight were measured at baseline and a 6‐month follow‐up. Baseline minimum dietary diversity (MDD) for children 6–23 months old was defined by consumption of five or more of the following food groups: (1) breast milk; (2) grains, roots and tubers; (3) legumes and nuts; (4) dairy products; (5) flesh foods; (6) eggs; (7) vitamin A‐rich fruits and vegetables and (8) other fruits and vegetables. Participants were 117 children 6–23 months of age. Linear growth faltering was defined as a significant decline (p < 0.05) in length‐for‐age Z‐scores (LAZ) between baseline and follow‐up. Regression models were performed. The study was conducted in rural eastern Democratic Republic of the Congo (DRC). MDD was positively associated with change in LAZ (coefficient: 0.87 [95% confidence interval [CI]: 0.33, 1.40]), and a reduced odds of stunting (LAZ < −2) (odds ratio: 0.21 [95% CI: 0.07, 0.61]). MDD was also associated with a significantly higher combined EASQ‐Z‐scores (coefficient: 0.34 [95% CI: 0.003, 0.68], higher communication EASQ‐Z‐scores [0.50 {95% CI: 0.14, 0.85}], and higher personal social EASQ‐Z‐scores [0.46 {95% CI: 0.11, 0.82}]). This study provides further evidence demonstrating the need for interventions to improve dietary diversity among young children.
Stiffness- and Bioactive Factor-Mediated Protection of Self-Assembled Cartilage against Macrophage Challenge in a Novel Co-Culture System

Objective: Tissue-engineered cartilage implants must withstand the potential inflammatory and joint loading environment for successful long-term repair of defects. The work’s objectives were to develop a novel, direct cartilage-macrophage co-culture system and to characterize interactions between self-assembled neocartilage and differentially stimulated macrophages. Design: In study 1, it was hypothesized that the proinflammatory response of macrophages would intensify with increasing construct stiffness; it was expected that the neocartilage would display a decrease in mechanical properties after co-culture. In study 2, it was hypothesized that bioactive factors would protect neocartilage properties during macrophage co-culture. Also, it was hypothesized that interleukin 10 (IL-10)-stimulated macrophages would improve neocartilage mechanical properties compared to lipopolysaccharide (LPS)-stimulated macrophages. Results: As hypothesized, stiffer neocartilage elicited a heightened proinflammatory macrophage response, increasing tumor necrosis factor alpha (TNF-α) secretion by 5.47 times when LPS-stimulated compared to construct-only controls. Interestingly, this response did not adversely affect construct properties for the stiffest neocartilage but did correspond to a significant decrease in aggregate modulus for soft and medium stiffness constructs. In addition, bioactive factor-treated constructs were protected from macrophage challenge compared to chondrogenic medium-treated constructs, but IL-10 did not improve neocartilage properties, although stiff constructs appeared to bolster the anti-inflammatory nature of IL-10-stimulated macrophages. However, co-culture of bioactive factor-treated constructs with LPS-treated macrophages reduced TNF-α secretion by over 4 times compared to macrophage-only controls. Conclusions: In conclusion, neocartilage stiffness can mediate macrophage behavior, but stiffness and bioactive factors prevent macrophage-induced degradation. Ultimately, this co-culture system could be utilized for additional studies to develop the burgeoning field of cartilage mechano-immunology.
Risk factors associated with diabetes after liver transplant

ABSTRACT Objective: Post-transplant diabetes mellitus (PTDM) is a common metabolic complication after liver transplant that negatively affects a recipient's survival and graft function. This study aims to identify risk factors associated with diabetes after liver transplant. Materials and methods: This is a cross-sectional study conducted from September to November 2019. Data collection was performed by chart review, and patients were divided into 3 groups: patients without diabetes mellitus (DM), patients with pre-transplant diabetes mellitus, and patients with PTDM. Results: Two hundred and forty-seven patients’ medical charts were screened, and 207 patients were included: 107 without DM, 42 with pre-transplant DM, and 58 with PTDM. The leading cause for liver transplant was hepatitis C, followed by hepatocellular carcinoma secondary to alcohol. There was a higher exposure to tacrolimus in patients without DM ( P = 0.02) and to ciclosporin in patients with pre-transplant DM, compared to others ( P = 0.005). Microscopic interface inflammatory activity was more severe in patients without DM as well as those with PTDM ( P = 0.032). There was a higher prevalence of steatosis in recipients with pre-transplant DM than there was in others ( P < 0.001). Multivariate logistic regression identified the following independent risk factors for DM: cirrhosis due to alcohol, hepatitis C, and triglycerides. For PTDM, these independent risk factors were cirrhosis due to alcohol, hepatitis C, and prednisone exposure. Conclusion: Alcoholic cirrhosis is a risk factor for PTDM in liver recipients. Liver transplant recipients with a pre-transplant history of cirrhosis due to alcohol, hepatitis C, and prednisone exposure deserve more caution during PTDM screening.
Bioactive compounds: a goldmine for defining new strategies against pathogenic bacterial biofilms?

Abstract Most human infectious diseases are caused by microorganisms growing as biofilms. These three-dimensional self-organized communities are embedded in a dense matrix allowing microorganisms to persistently inhabit abiotic and biotic surfaces due to increased resistance to both antibiotics and effectors of the immune system. Consequently, there is an urgent need for novel strategies to control biofilm-associated infections. Natural products offer a vast array of chemical structures and possess a wide variety of biological properties; therefore, they have been and continue to be exploited in the search for potential biofilm inhibitors with a specific or multi-locus mechanism of action. This review provides an updated discussion of the major bioactive compounds isolated from several natural sources – such as plants, lichens, algae, microorganisms, animals, and humans – with the potential to inhibit biofilm formation and/or to disperse established biofilms by bacterial pathogens. Despite the very large number of bioactive products, their exact mechanism of action often remains to be clarified and, in some cases, the identity of the active molecule is still unknown. This knowledge gap should be filled thus allowing development of these products not only as novel drugs to combat bacterial biofilms, but also as antibiotic adjuvants to restore the therapeutic efficacy of current antibiotics.
On the body‐mind nexus in chronic musculoskeletal pain: A scoping review

Bodily experience disturbances are frequent among chronic musculoskeletal pain patients and associated with important pain‐related psychosocial outcomes (e.g., disability, quality of life). However, the relationship between bodily experience and the psychological dimensions of chronic pain (e.g., affective, cognitive) has only recently garnered attention. This scoping review aimed to identify trends and gaps in research on the nexus between body awareness, body image, and body schema, and psychological processes/outcomes in adults with chronic musculoskeletal pain to inform future directions for research and practice.
John Charlton Polkinghorne KBE. 16 October 1930—9 March 2021

John Polkinghorne made many contributions to theoretical elementary particle physics. Between 1959 and 1979 he led the theoretical physics group in the Department of Applied Mathematics and Theoretical Physics in Cambridge University. He discovered important features of the analytic properties of the scattering matrix, culminating in the jointly authored book, The analytic S-matrix, which has become widely influential. He also worked on scattering at high energies and developed a covariant formulation of Feynman's (Richard Feynman ForMemRS) parton model (partons being later identified as quarks and gluons). In 1979, he resigned from his professorship of Mathematical Physics and commenced training as an Anglican priest. While serving in a number of appointments within the Church of England and then within Cambridge University he became one of the most influential figures in the growing academic field of science and religion, publishing both popular and academic texts and lecturing on an international stage.
Effectiveness of implementing a preventive urinary catheter care bundle in hip fracture patients

Background Urinary catheter (UC)–associated infections are one of the most common preventable healthcare-associated infections (HAIs) and they frequently occur in older, frail populations. Aim The study aim was to describe the incidence of UC-associated infection in elderly patients undergoing hip fracture surgery after implementing a preventive care bundle. Methods A longitudinal prospective study using a before-and-after design. The bundle was theory driven and involved the co-creation of a standard operational procedure, education and practical training sessions. Prospectively collected registry data were analysed. Univariable statistics and multivariable logistic regressions were used for analyses. Results 2,408 patients with an acute hip fracture were included into the study. There was an overall reduction in UC catheter associated-associated urinary tract infections, from 18.5% (n = 75/406) over time to 4.2% (n = 27/647). When adjusting for all identified confounders, patients in phase 4 were 74% less likely to contract an UC-associated infection (OR, 0.26; 95% CI, 0.15–0.45, p < 0.0001). Discussion Bundled interventions can reduce UC-associated infections substantially, even in elderly frail patients. Partnership and co-creation as implementation strategies appear to be promising in the fight against HAI.
Dynamic Probabilistic Graphical Model for Progressive Fake News Detection on Social Media Platform

Recently, fake news has been readily spread by massive amounts of users in social media, and automatic fake news detection has become necessary. The existing works need to prepare the overall data to perform detection, losing important information about the dynamic evolution of crowd opinions, and usually neglect the issue of uneven arrival of data in the real world. To address these issues, in this article, we focus on a kind of approach for fake news detection, namely progressive detection, which can be achieved by the dynamic Probabilistic Graphical Model. Based on the observation on real-world datasets, we adaptively improve the Kalman Filter to the Labeled Variable Dimension Kalman Filter (LVDKF) that learns two universal patterns from true and fake news, respectively, which can capture the temporal information of time-series data that arrive unevenly. It can take sequential data as input, distill the dynamic evolution knowledge regarding a post, and utilize crowd wisdom from users’ responses to achieve progressive detection. Then we derive the formulas using the Forward, Backward, and EM Algorithm, and we design a dynamic detection algorithm using Bayes’ theorem. Finally, we design experimental scenarios simulating progressive detection and evaluate LVDKF on two public datasets. It outperforms the baseline methods in these experimental scenarios, which indicates that it is adequate for progressive detection.
Measuring 9 Emotions of News Posts from 8 News Organizations across 4 Social Media Platforms for 8 Months

Using Plutchik’s wheel of emotions framework, we identify the emotional content of 133,487 social media posts and the audience’s emotional engagement expressed in 2,824,162 comments on those posts. We measure nine emotions (anger, anticipation, anxiety, disgust, joy, fear, sadness, surprise, trust) and two sentiments (positive and negative) using two extraction resources (EmoLex, LIWC) for eight major news outlets across four social media platforms (Facebook, Instagram, Twitter, and YouTube) during eight months. We then apply two approaches (Logistic Regression, Long Short-Term Memory) to predict emotional audience reactions before and after publishing the posts. Findings show significant differences for positive emotions but not for negative in the comments among the platforms. F1-scores for predicting emotional audience engagement are more than 70% for some emotions for some news outlets. Implications are that news outlets have leverage in steering emotional engagement for posts on social media platforms. The findings have theoretical and practical implications for understanding the complex emotional and informational interplay among social media content, platforms, and audiences.
Nucleic acids movement and its relation to genome dynamics of repetitive DNA

There is growing evidence of evolutionary genome plasticity. The evolution of repetitive DNA elements, the major components of most eukaryotic genomes, involves the amplification of various classes of mobile genetic elements, the expansion of satellite DNA, the transfer of fragments or entire organellar genomes and may have connections with viruses. In addition to various repetitive DNA elements, a plethora of large and small RNAs migrate within and between cells during individual development as well as during evolution and contribute to changes of genome structure and function. Such migration of DNA and RNA molecules often results in horizontal gene transfer, thus shaping the whole genomic network of interconnected species. Here, we propose that a high evolutionary dynamism of repetitive genome components is often related to the migration/movement of DNA or RNA molecules. We speculate that the cytoplasm is probably an ideal compartment for such evolutionary experiments.
Genetic analysis suggests a surface of PAT-4 (ILK) that interacts with UNC-112 (kindlin)

The transmembrane protein integrin plays a crucial role in the attachment of cells to the extracellular matrix. Integrin recruits many proteins intracellularly, including a four protein complex (Kindlin, Integrin linked kinase (ILK), PINCH, and parvin). C. elegans muscle provides an excellent model to study integrin adhesion complexes. In C. elegans, UNC-112 (Kindlin) binds to the cytoplasmic tail of PAT-3 (β-integrin) and to PAT-4 (ILK). We previously reported that PAT-4 binding to UNC-112 is essential for the binding of UNC-112 to PAT-3. Although there are crystal structures for ILK and a kindlin, there is no co-crystal structure available. To understand the molecular interaction between PAT-4 (ILK) and UNC-112 (Kindlin), we took a genetic approach. First, we isolated mutant PAT-4 proteins that cannot bind to UNC-112. Then, we isolated suppressor mutant UNC-112 proteins that restore interaction with mutant PAT-4 proteins. Second, these mutant PAT-4 proteins cannot localize to attachment structures in nematode muscle, but upon co-expression of an UNC-112 suppressor mutant protein, the mutant PAT-4 protein could localize to attachment structures. Third, overexpression of a mutant PAT-4 protein results in disorganization of the adhesion plaques at muscle cell boundaries, and co-expression of the UNC-112 supressor mutant protein alleviates this defect. Thus, we demonstrate that UNC-112 binding to PAT-4 is required for the localization and function of PAT-4 in integrin adhesion complexes in vivo. The missense mutations were mapped onto homology models of PAT-4 and UNC-112, and taking into account previously isolated mutations, we suggest a surface of PAT-4 that binds to UNC-112.