Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Mitochondrial Genome Analysis of Two Ectomycorrhizal Fungi (Rhizopogon) Reveals Dynamic Changes of Intron and Phylogenetic Relationships of the Subphylum Agaricomycotina

In the present study, we assembled and compared two mitogenomes from the Rhizopogon genus. The two mitogenomes of R. salebrosus and R. vinicolor comprised circular DNA molecules, with the sizes of 66,704 bp and 77,109 bp, respectively. Comparative mitogenome analysis indicated that the length and base composition of protein coding genes (PCGs), rRNA genes and tRNA genes varied between the two species. Large fragments aligned between the mitochondrial and nuclear genomes of both R. salebrosus (43.41 kb) and R. vinicolor (12.83 kb) indicated that genetic transfer between mitochondrial and nuclear genomes has occurred over evolutionary time of Rhizopogon species. Intronic regions were found to be the main factors contributing to mitogenome expansion in R. vinicolor. Variations in the number and type of introns in the two mitogenomes indicated that frequent intron loss/gain events occurred during the evolution of Rhizopogon species. Phylogenetic analyses based on Bayesian inference (BI) and Maximum likelihood (ML) methods using a combined mitochondrial gene set yielded identical and well-supported tree topologies, wherein Rhizopogon species showed close relationships with Agaricales species. This is the first study of mitogenomes within the genus Rhizopogon, and it provides a basis for understanding the evolution and differentiation of mitogenomes from the ectomycorrhizal fungal genus.
Natural Product Medicines for Honey Bees: Perspective and Protocols

The western honey bee remains the most important pollinator for agricultural crops. Disease and stressors threaten honey bee populations and productivity during winter- and summertime, creating costs for beekeepers and negative impacts on agriculture. To combat diseases and improve overall bee health, researchers are constantly developing honey bee medicines using the tools of microbiology, molecular biology and chemistry. Below, we present a manifesto alongside standardized protocols that outline the development and a systematic approach to test natural products as ‘bee medicines’. These will be accomplished in both artificial rearing conditions and in colonies situated in the field. Output will be scored by gene expression data of host immunity, bee survivorship, reduction in pathogen titers, and more subjective merits of the compound in question. Natural products, some of which are already encountered by bees in the form of plant resins and nectar compounds, provide promising low-cost candidates for safe prophylaxis or treatment of bee diseases.
Assessment of Functional Performance in Acute Geriatric Psychiatry – Time for New Strategies?

Objectives: The aim of this study was to investigate the feasibility and reliability of functional performance tests in people living with dementia and depression. Method: A cross-sectional study was conducted in a geriatric psychiatry hospital. People living with dementia, depression, and healthy older adults were included. Feasibility of the timed up and go test (TUG), the short physical performance battery (SPPB), and the multisurface obstacle test for older adults (MSOT) was assessed based on valid test executions. Test-retest reliability was evaluated by mean difference (MD), coefficient of variation (CV), standardized MD, intraclass correlation coefficient (ICC), and correlation coefficient (rs ). Results: A total of 53 people in acute geriatric psychiatry and 21 healthy older adults were included. In people living with dementia (n = 23), feasibility was 65.2% (MSOT), 8.7% (TUG), and 8.7% (SPPB). In people living with depression (n = 30), feasibility was 83.3% (MSOT), 80.0% (TUG), and 46.7% (SPPB). Intraclass correlation coefficients and rs for the MSOT were high (ICC > 0.70) in both groups. Coefficient of variations of the MSOT were between 10.7% and 18.0% (dementia) and 7.1% and 17.0% (depression). Reliability of the TUG and SPPB was not analyzed in people living with dementia, due to low feasibility. In people living with depression, ICCs and rs were between 0.86 and 0.87 with CVs of 7.2% (TUG) and 0.69 and 0.95 with CVs of 7.8% and 15.1% (SPPB). Conclusion: Feasibility and reliability of established functional performance tests in acute geriatric psychiatry are limited, especially in people living with dementia. New strategies, for example, sensor-based approaches, may allow measurement of functional performance apart from standardized instruction-based test procedures in this clinical population.
Genome Sequencing of Streptomyces olivaceus SCSIO T05 and Activated Production of Lobophorin CR4 via Metabolic Engineering and Genome Mining

Marine-sourced actinomycete genus Streptomyces continues to be an important source of new natural products. Here we report the complete genome sequence of deep-sea-derived Streptomyces olivaceus SCSIO T05, harboring 37 putative biosynthetic gene clusters (BGCs). A cryptic BGC for type I polyketides was activated by metabolic engineering methods, enabling the discovery of a known compound, lobophorin CR4 (1). Genome mining yielded a putative lobophorin BGC (lbp) that missed the functional FAD-dependent oxidoreductase to generate the d-kijanose, leading to the production of lobophorin CR4 without the attachment of d-kijanose to C17-OH. Using the gene-disruption method, we confirmed that the lbp BGC accounts for lobophorin biosynthesis. We conclude that metabolic engineering and genome mining provide an effective approach to activate cryptic BGCs.
Enhancer Dysfunction in 3D Genome and Disease

Spatiotemporal patterns of gene expression depend on enhancer elements and other factors during individual development and disease progression. The rapid progress of high-throughput techniques has led to well-defined enhancer chromatin properties. Various genome-wide methods have revealed a large number of enhancers and the discovery of three-dimensional (3D) genome architecture showing the distant interacting mechanisms of enhancers that loop to target gene promoters. Whole genome sequencing projects directed at cancer have led to the discovery of substantial enhancer dysfunction in misregulating gene expression and in tumor initiation and progression. Results from genome-wide association studies (GWAS) combined with functional genomics analyses have elucidated the functional impacts of many cancer risk-associated variants that are enriched within the enhancer regions of chromatin. Risk variants dysregulate the expression of enhancer variant-associated genes via 3D genomic interactions. Moreover, these enhancer variants often alter the chromatin binding affinity for cancer-relevant transcription factors, which in turn leads to aberrant expression of the genes associated with cancer susceptibility. In this review, we investigate the extent to which these genetic regulatory circuits affect cancer predisposition and how the recent development of genome-editing methods have enabled the determination of the impacts of genomic variation and alteration on cancer phenotype, which will eventually lead to better management plans and treatment responses to human cancer in the clinic.
Point Set Registration With Similarity and Affine Transformations Based on Bidirectional KMPE Loss

Robust point set registration is a challenging problem, especially in the cases of noise, outliers, and partial overlapping. Previous methods generally formulate their objective functions based on the mean-square error (MSE) loss and, hence, are only able to register point sets under predefined constraints (e.g., with Gaussian noise). This article proposes a novel objective function based on a bidirectional kernel mean ${p}$ -power error (KMPE) loss, to jointly deal with the above nonideal situations. KMPE is a nonsecond-order similarity measure in kernel space and shows a strong robustness against various noise and outliers. Moreover, a bidirectional measure is applied to judge the registration, which can avoid the ill-posed problem when a lot of points converges to the same point. In particular, we develop two effective optimization methods to deal with the point set registrations with the similarity and the affine transformations, respectively. The experimental results demonstrate the effectiveness of our methods.
Apalutamide Sensitizes Prostate Cancer to Ionizing Radiation via Inhibition of Non-Homologous End-Joining DNA Repair

Androgen-deprivation therapy was shown to improve treatment outcome of external beam radiation therapy (EBRT) for locally advanced prostate cancer (PCa). DNA damage response (DDR) was suggested to play a role in the underlying mechanism, but conflicting results were reported. This study aims to reveal the role of the androgen receptor (AR) in EBRT-induced DDR and to investigate whether next-generation AR inhibitor apalutamide can radiosensitize PCa. PCa cell lines and tissue slices were treated with anti-androgen alone or combined with EBRT. The effect of treatments on cell growth, tissue viability, DDR, and cell cycle were investigated. RAD51 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) levels were determined by Western blotting. Homologous recombination (HR) capacity was measured with the directed repeats-green fluorescent protein (DR-GFP) assay. We report the radiosensitizing effect of anti-androgens, which showed synergism in combination with EBRT in AR-expressing tumor slices and cell lines. Moreover, a compromised DDR was observed in AR-expressing cells upon AR suppression. We found that AR inhibition downregulated DNA-PKcs expression, resulting in reduced non-homologous end-joining repair. DDR through HR was a secondary effect due to cell-cycle change. These data provide a mechanistic explanation for the combination regimen and support the clinical use of apalutamide together with EBRT for localized PCa patients.
Anti-inflammatory Compound Shows Therapeutic Safety and Efficacy against Flavivirus Infection

Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus, and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of effort, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika virus pathogenesis. ABSTRACT Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus, and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of effort, we have no clinically specific therapeutic drugs against DENV and ZIKV. Previous studies showed that inflammatory responses play a critical role in dengue and Zika virus pathogenesis. Thus, in this study, we examined a series of novel anti-inflammatory compounds and found that treatment with compound 2d could dose dependently reduce viral protein expression and viral progeny production in HEK-293 and Raw264.7 cells infected with four serotypes of DENV and ZIKV. In addition, considering medication safety, compound 2d could not suppress cyclooxygenase-1 (COX-1) enzymatic activities and thus could prevent the side effect of bleeding. Moreover, compound 2d significantly inhibited COX-2 enzymatic activities and prostaglandin E2 levels, associated with viral replication, compared to results with a selective COX-2 inhibitor, celecoxib. Furthermore, administering 5 mg/kg compound 2d to DENV-2-infected AG129 mice prolonged survival and reduced viremia and serum cytokine levels. Overall, compound 2d showed therapeutic safety and efficacy in vitro and in vivo and could be further developed as a potential therapeutic agent for flavivirus infection.
Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin

Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.
Predictors of episodic migraine transformation to chronic migraine: A systematic review and meta-analysis of observational cohort studies

Background and purpose An estimated 2.5–3.1% of people with episodic migraine develop chronic migraine in a year. Several risk factors are associated with an increased risk for this transformation. We conducted a systematic review and meta-analysis to provide quantitative and qualitative data on predictors of this transformation. Methods An electronic search was conducted for published, prospective, cohort studies that reported risk factors for chronic migraine among people with episodic migraine. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. Quality of evidence was determined according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Effect estimates were retrieved and summarized using risk ratios. Results Of 5695 identified publications, 11 were eligible for inclusion. The pooled analysis (GRADE system) found “high” evidence for monthly headache day frequency ≥ 10 (risk ratio = 5.95), “moderate” evidence for depression (risk ratio = 1.58), monthly headache day frequency ≥ 5 (risk ratio = 3.18), and annual household income ≥ $50,000 (risk ratio = 0.65) and “very low” evidence for allodynia (risk ratio = 1.40) and medication overuse (risk ratio = 8.82) in predicting progression to chronic migraine. Conclusions High frequency episodic migraine and depression have high quality evidence as predictors of the transformation from episodic migraine to chronic migraine, while annual household income over $50,000 may be protective.
Effects of early trauma and corticotropin‐releasing factor receptor 1 gene polymorphism on adult visual spatial memory

The study sought to determine the effects of earthquake on the working memory of adults who experienced earthquake either as infants or fetuses and also investigates whether earthquake exposure and corticotropin‐releasing factor receptor 1 (CRHR1) variants rs242924 and rs7209436 interacted with each other in modulating working memory.
Noninferiority testing for matched‐pair ordinal data with misclassification

New treatments that are noninferior or equivalent to—but not necessarily superior to—the reference treatment may still be beneficial to patients because they have fewer side effects, are more convenient, take less time, or cost less. The noninferiority test is widely used in medical research to provide guidance in such situation. In addition, categorical variables are frequently encountered in medical research, such as in studies involving patient‐reported outcomes. In this paper, we develop a noninferiority testing procedure for correlated ordinal categorical variables based on a paired design with a latent normal distribution approach. Misclassification is frequently encountered in the collection of ordinal categorical data; therefore, we further extend the procedure to account for misclassification using information in the partially validated data. Simulation studies are conducted to investigate the accuracy of the estimates, the type I error rates, and the power of the proposed procedure. Finally, we analyze one substantive example to demonstrate the utility of the proposed approach.
Negative Life Events and Suicide in the National Violent Death Reporting System

Objective Negative life events may be a major precipitating factor for suicide and may differ across sociodemographic groups. We used data from the National Violent Death Reporting System (NVDRS) to explore whether age, gender, current mental illness, and disclosure around suicide predicted adult decedents’ precipitants for suicide. Method: An NVDRS data set was used that included 58,247 adults who died by suicide between 2005 and 2010. Multivariate logistic regression was used to explore the relationship between sociodemographic characteristics and precipitating factors while controlling for the impact of other factors. Results: Age group (18–34, 35–64, or ≥ 65), sex, current mental illness, and disclosure around suicide significantly predicted various precipitants. Males were more likely than females to have most precipitating factors, particularly a criminal legal problem (odds ratio [OR]: 2.76), job problem (OR: 1.97), or financial problem (OR: 1.42). While younger decedents had more crises and intimate partner problems, middle-aged decedents had more loss of housing (OR: 1.87) and financial (OR: 1.81) and job-related (OR: 1.35) precipitants than the younger group. The odds of a physical health issue increased successively with each age group. Identified mental illness was associated most strongly with a job (OR: 1.43) or physical health problem (OR: 1.35). Individuals who disclosed suicidal ideation had a higher incidence of all precipitants. Conclusions: The precipitants to suicide appear to vary according to individuals’ demographic factors, current mental illness, and disclosure of intent. Our understanding of suicide may be enhanced by exploring the causal pathway behind these relationships.
Targeting Unique Epitopes on Highly Similar Proteins GDF-11 and GDF-8 with Modified DNA Aptamers.

The mature forms of the TGF-β family members GDF-11 and GDF-8 are highly similar 25 kDa homodimers with 90% amino acid sequence identity and 99% similarity. Cross-reactivity of GDF-11 and GDF-8 binding reagents is common making it difficult to attribute distinct roles of these two proteins in biology. We report the selection of GDF-11 and GDF-8 specific SOMAmer (Slow Off-rate Modified Aptamer) reagents aided by a combination of positive selection for one protein, coupled with counter-selection against the other. We identified GDF-11 specific SOMAmer reagents from four modified DNA libraries that showed a high affinity (Kd range, 0.05 - 1.2 nM) for GDF-11 but did not bind to GDF-8 (Kd >1 µM). Conversely, we identified one SOMAmer reagent for GDF-8 from one of the modified libraries that demonstrated excellent affinity (Kd = 0.23 nM) and specificity. In contrast, standard protocols that utilized only positive selection produced binding reagents with similar affinity for both proteins. High affinity and specificity were efficiently encoded in minimal sequences of 21 nucleotides for GDF-11 and 24 nucleotides for GDF-8. Further characterization in pull-down, competition, sandwich-binding, and kinetic studies revealed robust binding under a wide range of buffer and assay conditions. For highly similar proteins like GDF-11 and GDF-8, our method of selection coupled with counter-selection was essential for identification of high-affinity, specific reagents that have the potential to elucidate the fundamental distinction of these growth factors in biology.
Future Time Perspective in Mid-to-Later Life: The Role of Personality.

OBJECTIVES Future time perspective (FTP), or the way individuals orient to and consider their futures, is fundamental to motivation and well-being across the life span. There is a relative paucity of studies, however, that explore its contributing factors in mid-to-later life, specifically. Therefore, uncovering which variables contribute to individual differences in FTP, as well as the ways these variables interact, is paramount to developing a strong understanding of this construct during this life-span stage. METHOD This study used three data mining techniques (ie, elastic net, decision tree, and tree ensemble analyses) to simultaneously test several potential contributors identified in the literature, including the five-factor personality domains, several health indices, and age. RESULTS Personality, especially neuroticism, extraversion, conscientiousness, and agreeableness, had the most influence on FTP. Age and health were not among the most salient FTP contributors in mid-to-later life. Furthermore, decision tree analyses uncovered interactive effects of personality; several profiles of neuroticism, extraversion, and/or conscientiousness were linked with differing FTP levels. DISCUSSION Although the extant literature has indicated that FTP, age, and health are inextricably tied, these results indicate that there is more variability to be explained in FTP, perhaps especially when looking within specific age groups.
The long non-coding RNA GHSROS facilitates breast cancer cell migration and orthotopic xenograft tumour growth

Recent evidence suggests that numerous long non-coding RNAs (lncRNAs) are dysregulated in cancer, and have critical roles in tumour development and progression. The present study investigated the ghrelin receptor antisense lncRNA growth hormone secretagogue receptor opposite strand (GHSROS) in breast cancer. Reverse transcription-quantitative polymerase chain reaction revealed that GHSROS expression was significantly upregulated in breast tumour tissues compared with normal breast tissue. Induced overexpression of GHSROS in the MDA-MB-231 breast cancer cell line significantly increased cell migration in vitro, without affecting cell proliferation, a finding similar to our previous study on lung cancer cell lines. Microarray analysis revealed a significant repression of a small cluster of major histocompatibility class II genes and enrichment of immune response pathways; this phenomenon may allow tumour cells to better evade the immune system. Ectopic overexpression of GHSROS in the MDA-MB-231 cell line significantly increased orthotopic xenograft growth in mice, suggesting that in vitro culture does not fully capture the function of this lncRNA. This study demonstrated that GHSROS may serve a relevant role in breast cancer. Further studies are warranted to explore the function and therapeutic potential of this lncRNA in breast cancer progression.