Miracle-dz/UniFAR-FTUs huggingface dataset:
Multimodality treatment including ONCEPT for canine oral melanoma: A retrospective analysis of 131 dogs.

Canine oral melanoma (OM) is an aggressive cancer with a high rate of metastasis. Surgery and/or radiotherapy (RT) are effective local treatments, yet many dogs succumb to distant metastasis. Immunotherapy represents an attractive strategy for this potentially immunogenic tumor. The objective of this multi-institutional retrospective study was to examine the clinical outcome of dogs with OM treated with ONCEPT melanoma vaccine. Most dogs also underwent surgery and/or RT (8 Gy × four weekly fractions). Dogs with distant metastasis at diagnosis and those receiving concurrent chemotherapy were excluded. One hundred thirty-one dogs treated with ONCEPT were included: 62 had adequate local tumor control defined as complete tumor excision or irradiation of residual microscopic disease; 15 were treated in the microscopic disease setting following an incomplete excision without adjuvant RT; and 54 had gross disease. Median time to progression, median progression-free survival, and median tumor-specific overall survival were 304, 260, and 510 days, respectively. In multivariable analysis, presence of gross disease correlated negatively with all measures of clinical outcome. Other negative prognostic indicators were primary tumor ≥2 cm, higher clinical stage (stages 2 and 3), presence of lymph node metastasis at diagnosis, and caudal location in the oral cavity. Radiotherapy had a protective effect against tumor progression. To date, this is the largest reported series of dogs with OM treated with ONCEPT. Several previously reported prognostic indicators were confirmed.
Culture, Structure, and Health: Narratives of Low-income Bangladeshi Migrant Workers from the United Arab Emirates

ABSTRACT Increasingly, health scholars are paying attention to the health experiences of immigrant communities, particularly in the backdrop of the global flows of goods, services, and people across borders. In spite of the increasing public health emphasis on health outcomes of immigrants within the Middle Eastern (ME) countries, immigrant communities are often constructed as monoliths and the voices of immigrant communities are traditionally absent from mainstream health policy and program discourses. The health experiences of immigrants, their access to resources, and the health trajectories through the life-course followed by them and their descendants influence the deep-seated patterns of ethnic health disparities documented in the ME. Based on the culture-centered approach, we engaged in in-depth face-to-face interviews, and focus groups discussions with a total of 44 research participants, to understand how low-income Bangladeshi migrant workers in the United Arab Emirates (UAE), who live at the borders of mainstream Arab society, define, construct, and negotiate health issues. Participants articulate in their narratives their nuanced cultural understanding of good health as a complex, holistic practice, the achievement of which is obstructed by barriers such as immigration and insurance structures. Further, they enact their agency in resource impoverished circumstances to protect their mental health and physical well-being through daily strategies and acts of resistance.
Insights into the N6-methyladenosine mechanism and its functionality: progress and questions

Abstract N6-methyladenosine (m6A) RNA methylation has become a progressively popular area of molecular research since the discovery of its potentially essential regulatory role amongst eukaryotes. m6A marks are observed in the 5’UTR, 3’UTR and coding regions of eukaryotes and its mediation has been associated with various human diseases, RNA stability and translational efficiency. To understand the implications of m6A methylation in molecular governance, its functionality and mechanism must be initially understood. m6A regulation through its readers, writers and erasers as well as an insight into the potential “cross-talk” occurring between m6A and previously well documented regulatory molecular mechanisms have been characterized. The majority of research to date has been limited to few species and has yet to explore the species- and tissue specific nature or mechanistic plasticity of m6A regulation. There is still a tremendous gap in our knowledge surrounding the mechanism and functionality of m6A RNA methylation. Here we review the formation, removal, and decoding of m6A amongst animals, yeast, and plants while noting potential “cross-talk” between various mechanisms and highlighting potential areas of future research.
Tumor Fusion Burden as a Hallmark of Immune Infiltration in Prostate Cancer

Despite the link of tumor mutational burden with response to immunotherapy, it is not universal across tumor types. In prostate cancer, the burden of tumor gene fusions positively correlates with antitumor immunity, inversely correlating with tumor mutational burden. Prostate cancer is the second leading cause of cancer-related death in men. Despite having a relatively lower tumor mutational burden than most tumor types, multiple gene fusions such as TMPRSS2:ERG have been characterized and linked to more aggressive disease. Individual tumor samples have been found to contain multiple fusions, and it remains unknown whether these fusions increase tumor immunogenicity. Here, we investigated the role of fusion burden on the prevalence and expression of key molecular and immune effectors in prostate cancer tissue specimens that represented the different stages of disease progression and androgen sensitivity, including hormone-sensitive and castration-resistant prostate cancer. We found that tumor fusion burden was inversely correlated with tumor mutational burden and not associated with disease stage. High fusion burden correlated with high immune infiltration, PD-L1 expression on immune cells, and immune signatures, representing activation of T cells and M1 macrophages. High fusion burden inversely correlated with immune-suppressive signatures. Our findings suggest that high tumor fusion burden may be a more appropriate biomarker than tumor mutational burden in prostate cancer, as it more closely associates with immunogenicity, and suggests that tumors with high fusion burden could be potential candidates for immunotherapeutic agents.
Photopolymerizable hydrogel encapsulated fibromodulin-reprogrammed cells for muscle regeneration.

A central challenge in tissue engineering is obtaining a suitable cell type with a capable delivery vehicle to replace or repair damaged or diseased tissues with tissue mimics. Notably, for skeletal muscle tissue engineering, given the inadequate availability and regenerative capability of endogenous myogenic progenitor cells as well as the tumorigenic risks presented by the currently available pluri- and multipotent stem cells, seeking a safe regenerative cell source is urgently demanded. To conquer this problem, we previously established a novel reprogramming technology that can generate multipotent cells from dermal fibroblasts using a single protein, fibromodulin (FMOD). The yield FMOD-reprogrammed (FReP) cells exhibit exceeding myogenic capability without tumorigenic risk, making them a promising and safe cell source for skeletal muscle establishment. In addition to employing the optimal cell for implantation, it is equally essential to maintain cellular localization and retention in the recipient tissue environment for critical-sized muscle tissue establishment. In this study, we demonstrate that the photopolymerizable methacrylate glycol chitosan (MeGC)/type I collagen (ColI)-hydrogel provides a desirable microenvironment for encapsulated FReP cells survival, spreading, extension, and formation of myotubes in the hydrogel three-dimensionally in vitro, without undesired osteogenic, chondrogenic, or tenogenic differentiation. Furthermore, gene profiling revealed a paired box 7 (PAX7) → myogenic factor 5 (MYF5) → myogenic determination 1 (MYOD1) → myogenin (MYOG) → myosin cassette elevation in the encapsulated FReP cells during myogenic differentiation, which is similar to that of the predominant driver of endogenous skeletal muscle regeneration, satellite cells. These findings constitute the evidence that the FReP cell-MeGC/ColI-hydrogel construct is a promising tissue engineering mimic for skeletal muscle generation in vitro, and thus possesses the extraordinary potential for further in vivo validation.
Women’s lived experience of well-being in everyday life when living with a stress-related illness

ABSTRACT Purpose: The aim of the study was to describe how women with stress-related illness experience well-being in everyday life. Methods: The study was based on a reflective lifeworld research (RLR) approach and the methodological principles of openness, flexibility and bridling. Twelve women, aged 27–54 years, diagnosed with stress-related illness were included. Data were collected with lifeworld interviews based on photographs taken by the women relating to well-being in everyday life. The data were analysed for meaning. Results: Well-being emerged in situations where women could feel an unconditional beingness. This entails not having demands on oneself and includes some form of freedom from having to perform. The surroundings and supportive environments are important for this unconditional beingness to be present. In order to feel well-being in everyday life, the women need to balance their energy and find helpful tools that can achieve a balance in everyday life. Conclusions: Healthcare staff need to understand the importance of unconditional beingness in supportive environments for patients living with stress-related illness in order to support their health and well-being. It is also important to support patients in finding helpful tools that can aid them to achieve a balance in everyday life.
Circular RNA Circ100084 functions as sponge of miR-23a-5p to regulate IGF2 expression in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has become a major cause of cancer-related mortality worldwide. Circular RNAs (circRNAs) are non-coding RNAs that serve important roles in multiple cancers. However, the role of circRNAs in HCC remains largely unknown. In the present study, a circRNA microarray dataset of HCC samples, GSE97332, was downloaded from the gene expression omnibus database. Following data preprocessing, differentially expressed circRNAs between HCC tissues and normal tissues were determined using GEO2R. The circRNA-miRNA interactions were predicted by the miRanda database. The miRTarbase database was used to search for target genes of the miRNAs. A circRNA-miRNA-mRNA network was constructed using Cytoscape based on the obtained circRNA, miRNA and mRNA. In this network, the upregulated circRNA hsa_circRNA_100084 was found to be involved in a competing endogenous relationship of hsa_circRNA_100084-hsa-miR-23a-5p- insulin-like growth factor 2 (IGF2). The differential expression of hsa_circRNA_100084, hsa-miR-23a-5p and IGF2 in HCC tissues and liver cancer cells was validated by reverse transcription-quantitative PCR. Additionally, the interactions between hsa-miR-23a-5p with hsa_circRNA_100084 and IGF2 were validated by dual-luciferase reporter assays. Knocking down hsa_circRNA_100084 inhibited the proliferation, migration and invasion of liver cancer cells, while the simultaneous overexpression of IGF2 reversed the effects of hsa_circRNA_100084 knockdown. The results show that hsa_circRNA_100084 could promote the expression of IGF2 by acting as a sponge of hsa-miR-23a-5p in liver cancer cells.
Pre‐pubertal, low‐intensity exercise does not require concomitant venlafaxine to induce robust, late‐life antidepressant effects in Flinders sensitive line rats

A significant number of adolescents are considered insufficiently active. This is of concern considering the negative association between physical activity and major depressive disorder (MDD). There is a lack of approved pharmacological treatment options in this population partly due to limited information on the risks associated with lasting effects during early life. Therefore, interest in non‐pharmacological strategies is gaining popularity with low‐ to moderate‐intensity exercise being especially attractive for its antidepressant‐like effects and augmentation properties in combination with antidepressants. Early‐life development might present a unique “window of opportunity” to induce long‐term beneficial effects in individuals treated with central acting drugs, such as antidepressants. Therefore, we investigated the bio‐behavioural effects of pre‐pubertal, low‐intensity exercise (EXE) and/or venlafaxine (VEN) on depressive‐like behaviour in juvenile (postnatal day 35 (PND35)) and young adult (PND60) stress‐sensitive Flinders sensitive line (FSL) rats. Interventions were introduced during pre‐pubertal development, that is PND21‐34, followed by a 26‐day washout/sedentary period, when bio‐behavioural analyses were performed in the early adulthood group. VEN, alone or in combination with EXE, proved ineffective in inducing any bio‐behavioural changes in either age group. EXE did not induce early‐life antidepressant‐like effects, despite increasing frontal serotonin (5‐HT) and noradrenaline (NA) levels. Later in life (PND60), pre‐pubertal exercise reduced immobility and increased coping behaviours, together with increased cortical 5‐HT levels, despite a significant reduction in locomotor activity. These findings emphasize a strong serotonergic basis to the observed delayed antidepressant effects of EXE later in life.
The different antioxidant and anticancer activities depending on the color of oyster mushrooms.

Oyster mushroom is a popular edible mushroom which has various colorful fruit bodies. The objective of this study was to determine the antioxidant and the anticancer activities of oyster mushrooms (OM) with different colors such as dark-grey strain (Pleurotus ostreatus), yellow strain (Pleurotus cornucopiae), and pink strain (Pleurotus salmoneostramineus). The methanolic extracts from OMs were prepared for this study. Among these OMs, the extract from the yellow strain showed the highest radical scavenging activity, reducing power, ferrous chelating ability, and total phenolic contents. Radical scavenging activity of yellow strain was about 3 times higher than that of dark-grey strain. On the other hand, the extracts of dark-grey and pink strains showed higher suppressive effect against growth of human colon cancer cell line HT-29 with survival rates of 39.9 and 40.7%, respectively, than that of yellow strain. These results showed that the antioxidant and the anticancer activities of OMs varied by the colors of fruit bodies. Key words: Pleurotus species, oyster mushroom, antioxidant, anticancer.
Methyltransferase DnmA is responsible for genome-wide N6-methyladenosine modifications at non-palindromic recognition sites in Bacillus subtilis

Abstract The genomes of organisms from all three domains of life harbor endogenous base modifications in the form of DNA methylation. In bacterial genomes, methylation occurs on adenosine and cytidine residues to include N6-methyladenine (m6A), 5-methylcytosine (m5C), and N4-methylcytosine (m4C). Bacterial DNA methylation has been well characterized in the context of restriction-modification (RM) systems, where methylation regulates DNA incision by the cognate restriction endonuclease. Relative to RM systems less is known about how m6A contributes to the epigenetic regulation of cellular functions in Gram-positive bacteria. Here, we characterize site-specific m6A modifications in the non-palindromic sequence GACGmAG within the genomes of Bacillus subtilis strains. We demonstrate that the yeeA gene is a methyltransferase responsible for the presence of m6A modifications. We show that methylation from YeeA does not function to limit DNA uptake during natural transformation. Instead, we identify a subset of promoters that contain the methylation consensus sequence and show that loss of methylation within promoter regions causes a decrease in reporter expression. Further, we identify a transcriptional repressor that preferentially binds an unmethylated promoter used in the reporter assays. With these results we suggest that m6A modifications in B. subtilis function to promote gene expression.
Beyond the Michaelis‐Menten: Accurate Prediction of In Vivo Hepatic Clearance for Drugs With Low K M

Clearance (CL) is the major pharmacokinetic parameter for evaluating systemic exposure of drugs in the body and, thus, for developing new drugs. To predict in vivo CL, the ratio between the maximal rate of metabolism and Michaelis‐Menten constant (Vmax/KM estimated from in vitro metabolism study has been widely used. This canonical approach is based on the Michaelis‐Menten equation, which is valid only when the KM value of a drug is much higher than the hepatic concentration of the enzymes, especially cytochrome P450, involved in its metabolism. Here, we find that such a condition does not hold for many drugs with low KM, and, thus, the canonical approach leads to considerable error. Importantly, we propose an alternative approach, which incorporates the saturation of drug metabolism when concentration of the enzymes is not sufficiently lower than KM. This new approach dramatically improves the accuracy of prediction for in vivo CL of high‐affinity drugs with low KM. This indicates that the proposed approach in this study, rather than the canonical approach, should be used to predict in vivo hepatic CL for high‐affinity drugs, such as midazolam and propafenone.
Empathy, mentalizing, and cognitive functioning in anorexia nervosa and bulimia nervosa

ABSTRACT The existing evidence on the specific profile and the determinants of empathic and mentalizing abilities in anorexia nervosa (AN) and bulimia nervosa (BN) is not conclusive. Moreover, it is not clear whether patients with eating disorders also exhibit diminished ability to accurately appraise their own empathic skills. We examine in AN and BN: (a) the impairments in various aspects of empathy and theory of mind (ToM), while accounting for the effect of other cognitive functions and (b) the accuracy of self-appraisal of empathy. Self-reported and performance-based empathy, ToM, and cognitive functions were assessed in 46 patients with AN, 30 patients with BN, and 42 healthy controls (HC). Both AN and BN patients reported diminished overall empathic abilities, whereas only BN patients reported reduced cognitive empathy compared to HC. Deficits in performance-based empathy were found in both patient groups. Cognitive ToM was impaired only in AN. Significant correlations between self-reported and performance-based empathy were found in BN and HC but not in AN. Cognitive deficits negatively affected the self-appraisal of empathy in AN but not empathic skills per se. Our findings highlight a double deficit related to empathic responding in AN: diminished performance and inaccurate self-appraisal of empathic abilities, indicating dysfunctional self-reflection.
Retroviruses in the pathogenesis of systemic lupus erythematosus: Are they potential therapeutic targets?

Abstract The pathogenesis of systemic lupus erythematosus (SLE) is characterised by the hyper-activation of immunologic pathways related to the antiviral response. Exogenous and endogenous retroviruses, by integrating their DNA templates in the host cell genome, may epigenetically control the transcription of genes involved in the immune response. Furthermore, their nucleic acids or neo-synthesized proteins could stimulate the sensor molecules placed upstream the inflammatory cascade. Exogenous retroviruses, like human immunodeficiency virus, have been associated to SLE-like manifestations or to a fair SLE diagnosis. In addition, there is some evidence confirming a pathogenic role of human endogenous retroviruses in SLE. In line with these data, the use of antiretroviral agents could represent an attractive opportunity in the future therapeutic algorithms of this disease, but studies are still missing.
The Quality Assurance and Quality Control Protocol for Neuropsychological Data Collection and Curation in the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study

As large research initiatives designed to generate big data on clinical cohorts become more common, there is an increasing need to establish standard quality assurance (QA; preventing errors) and quality control (QC; identifying and correcting errors) procedures for critical outcome measures. The present article describes the QA and QC approach developed and implemented for the neuropsychology data collected as part of the Ontario Neurodegenerative Disease Research Initiative study. We report on the efficacy of our approach and provide data quality metrics. Our findings demonstrate that even with a comprehensive QA protocol, the proportion of data errors still can be high. Additionally, we show that several widely used neuropsychological measures are particularly susceptible to error. These findings highlight the need for large research programs to put into place active, comprehensive, and separate QA and QC procedures before, during, and after protocol deployment. Detailed recommendations and considerations for future studies are provided.
The role of serum Dickkopf‐1 in predicting 30‐day death in severe traumatic brain injury

Dickkopf‐1 (DKK‐1), an inhibitor of the canonical/‐catenin cascade of the Wnt pathway, was upregulated in brain tissues of hemorrhagic stroke rats, and its rising circulating levels were associated with poor prognosis of acute ischemic stroke patients. We attempted to ascertain the relationship between serum DKK‐1 levels and 30‐day death after severe traumatic brain injury (sTBI).
Are Antimicrobial Peptide Dendrimers an Escape from ESKAPE?

Significance: The crisis of antimicrobial resistance (AMR) increases dramatically despite all efforts to use available antibiotics or last resort antimicrobial agents. The spread of the AMR, declared as one of the most important health-related issues, warrants the development of new antimicrobial strategies. Recent Advances: Antimicrobial peptides (AMPs) and AMP dendrimers (AMPDs), as well as polymer dendrimers are relatively new and promising strategies with the potential to overcome drug resistance issues arising in ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) colonizing chronic wounds. Critical Issues: AMPs–AMPDs suffer from limited efficacy, short-lasting bioactivity, and concerns of toxicity. To circumvent these drawbacks, their covalent coupling to biopolymers and/or encapsulation into different drug carrier systems is investigated, with a special focus on topical applications. Future Directions: Scientists and the pharmaceutical industry should focus on this challenging subject to either improve the activity of existing antimicrobial agents or find new drug candidates. The focus should be put on the discovery of new drugs or the combination of existing drugs for a better synergy, taking into account all kinds of wounds and existing pathogens, and more specifically on the development of next-generation antimicrobial peptides, encompassing the delivery carrier toward improved pharmacokinetics and efficacy.