Miracle-dz/UniFAR-FTUs huggingface dataset:
N-acetylglucosamine Signaling: Transcriptional Dynamics of a Novel Sugar Sensing Cascade in a Model Pathogenic Yeast, Candida albicans

The amino sugar, N-acetylglucosamine (GlcNAc), has emerged as an attractive messenger of signaling in the pathogenic yeast Candida albicans, given its multifaceted role in cellular processes, including GlcNAc scavenging, import and metabolism, morphogenesis (yeast to hyphae and white to opaque switch), virulence, GlcNAc induced cell death (GICD), etc. During signaling, the exogenous GlcNAc appears to adopt a simple mechanism of gene regulation by directly activating Ngs1, a novel GlcNAc sensor and transducer, at the chromatin level, to activate transcriptional response through the promoter acetylation. Ngs1 acts as a master regulator in GlcNAc signaling by regulating GlcNAc catabolic gene expression and filamentation. Ndt80-family transcriptional factor Rep1 appears to be involved in the recruitment of Ngs1 to GlcNAc catabolic gene promoters. For promoting filamentation, GlcNAc adopts a little modified strategy by utilizing a recently evolved transcriptional loop. Here, Biofilm regulator Brg1 takes up the key role, getting up-regulated by Ngs1, and simultaneously induces Hyphal Specific Genes (HSGs) expression by down-regulating NRG1 expression. GlcNAc kinase Hxk1 appears to play a prominent role in signaling. Recent developments in GlcNAc signaling have made C. albicans a model system to understand its role in other eukaryotes as well. The knowledge thus gained would assist in designing therapeutic interventions for the control of candidiasis and other fungal diseases.
Potential Herb–Drug Interactions in the Management of Age-Related Cognitive Dysfunction

Late-life mild cognitive impairment and dementia represent a significant burden on healthcare systems and a unique challenge to medicine due to the currently limited treatment options. Plant phytochemicals have been considered in alternative, or complementary, prevention and treatment strategies. Herbals are consumed as such, or as food supplements, whose consumption has recently increased. However, these products are not exempt from adverse effects and pharmacological interactions, presenting a special risk in aged, polymedicated individuals. Understanding pharmacokinetic and pharmacodynamic interactions is warranted to avoid undesirable adverse drug reactions, which may result in unwanted side-effects or therapeutic failure. The present study reviews the potential interactions between selected bioactive compounds (170) used by seniors for cognitive enhancement and representative drugs of 10 pharmacotherapeutic classes commonly prescribed to the middle-aged adults, often multimorbid and polymedicated, to anticipate and prevent risks arising from their co-administration. A literature review was conducted to identify mutual targets affected (inhibition/induction/substrate), the frequency of which was taken as a measure of potential interaction. Although a limited number of drugs were studied, from this work, interaction with other drugs affecting the same targets may be anticipated and prevented, constituting a valuable tool for healthcare professionals in clinical practice.
Identification and Mapping of Tomato Genome Loci Controlling Tolerance and Resistance to Tomato Brown Rugose Fruit Virus

Tomato brown rugose fruit virus (ToBRFV) was identified in Israel during October 2014 in tomato plants (Solanum lycopersicum). These plants, carrying the durable resistance gene against tomato mosaic virus, Tm-22, displayed severe disease symptoms and losses to fruit yield and quality. These plants were found infected with a tobamovirus similar to that discovered earlier in Jordan. This study was designed to screen and identify tomato genotypes resistant or tolerant to ToBRFV. The identified resistance and tolerance traits were further characterized virologically and genetically. Finally, DNA markers linked to genes controlling these traits were developed as tools to expedite resistance breeding. To achieve these objectives, 160 genotypes were screened, resulting in the identification of an unexpectedly high number of tolerant genotypes and a single genotype resistant to the virus. A selected tolerant genotype and the resistant genotype were further analyzed. Analysis of genetic inheritance revealed that a single recessive gene controls tolerance whereas at least two genes control resistance. Allelic test between the tolerant and the resistant genotype revealed that these two genotypes share a locus controlling tolerance, mapped to chromosome 11. This locus displayed a strong association with the tolerance trait, explaining nearly 91% of its variation in segregating populations. This same locus displayed a statistically significant association with symptom levels in segregating populations based on the resistant genotype. However, in these populations, the locus was able to explain only ~41% of the variation in symptom levels, confirming that additional loci are involved in the genetic control of the resistance trait in this genotype. A locus on chromosome 2, at the region of the Tm-1 gene, was finally found to interact with the locus discovered on chromosome 11 to control resistance.
Anxiety and Depressive Disorders in Children Born Preterm: A Meta-Analysis.

OBJECTIVE Preterm birth is associated with a high prevalence of psychiatric disorders including internalizing problems. However, there is a lack of consensus on the risk for depression and on specific diagnostic profiles. This meta-analysis investigates the independent pooled odds of Diagnostic and Statistical Manual of Mental Disorders Fourth Edition anxiety and depressive disorders in children between 3 and 19 years of age born preterm compared with their term-born peers. METHOD PubMed/MEDLINE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature electronic databases were searched (last updated in September 2019) using population ("child"), exposure ("preterm birth"), and outcome ("anxiety") terms for English peer-reviewed publications. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed with the risk of bias assessed using the Newcastle-Ottawa Quality Assessment Scale. Pooled odds ratio (OR) with 95% confidence intervals (CIs) was estimated using fixed-effects models. RESULTS Eleven independent studies met the inclusion criteria. The pooled sample comprised 1294 preterm and 1274 term-born children with anxiety outcomes and 777 preterm and 784 term-born children with depressive outcomes between 3 and 19 years of age. Children born preterm had significantly greater odds for anxiety (OR: 2.17; 95% CI, 1.43-3.29), generalized anxiety (OR: 2.20; 95% CI, 1.26-3.84), and specific phobia (OR: 1.93; 95% CI, 1.05-3.52) relative to their term-born peers. There were no significant between-group differences for reported depressive disorders. CONCLUSION Preterm birth is associated with a higher prevalence of anxiety, but not depressive disorders, from 3 to 19 years of age, suggesting distinct etiological pathways in this high-risk population. The findings support variation in the rates of specific anxiety diagnoses, indicating the need to extend neurodevelopmental surveillance to encompass a holistic emotional screening approach.
Prediction of Calving to Conception Interval Length Using Algorithmic Analysis of Endometrial mRNA Expression in Bovine

Simple Summary Our study aimed to develop the unsupervised clustering model based solely on selected markers to investigate the association between calving conception interval length, subclinical endometritis, and endometrial gene expression. An algorithmic analysis of endometrial gene expression showed a higher predictive ability to identify cows exhibiting excellent fertility than previously used methods, highlighting the correlation between INHBA/INHA and calving–conception interval length. Abstract After parturition, the uterus undergoes significant reconstruction, allows the endometrium to create an environment for subsequent embryo development. Here, we used an unsupervised algorithmic approach to select characteristic endometrial mRNA expression patterns of proposed markers and investigate each marker’s role as an individual indicator of reproductive success. Clinically healthy cows at a sixth week postpartum were examined, the percentage of neutrophils (PMNs%) in the cytological smear was calculated, and an endometrial biopsy was taken for qPCR. Based on pregnancy examination, cows were divided into three groups: Pregnant before 100 days postpartum (P100, n = 11), pregnant between 100–200-day (P200, n = 14), and culled (C, n = 10). Animals were also classified based on two PMNs% thresholds > 5% PMNs and > 10% PMNs. The expression of IL1B, IL6, CXCL8, and IL17A was higher in >10%PMNs. The expression of PTGS1 was higher in the P200 compared to P100. Upregulation of inhibin A subunit (INHA) and downregulation of inhibin β A subunit (INHBA) were observed in the P100. INHBA/INHA ratio was the most accurate linear predictor of the calving-to-conception interval. The application of the k-means algorithm allowed the identification of five unique expression patterns. The sensitivity and specificity of predicting allocation to P100 were 81% and 79%. We also documented the low efficiency of genes associated with subclinical endometritis and PMNs% in determining reproductive capability. These results suggested the presence of distinctive expression patterns in 6 weeks postpartum, correlated with cows’ reproductive capacity. Furthermore, we proposed the INHBA/INHA ratio as an indicator of calving-to-conception interval length.
Facile Bio-Fabrication of Ag-Cu-Co Trimetallic Nanoparticles and Its Fungicidal Activity against Candida auris

Candida auris is an emergent multidrug-resistant pathogen that can lead to severe bloodstream infections associated with high mortality rates, especially in hospitalized individuals suffering from serious medical problems. As Candida auris is often multidrug-resistant, there is a persistent demand for new antimycotic drugs with novel antifungal action mechanisms. Here, we reported the facile, one-pot, one-step biosynthesis of biologically active Ag-Cu-Co trimetallic nanoparticles using the aqueous extract of Salvia officinalis rich in polyphenols and flavonoids. These medicinally important phytochemicals act as a reducing agent and stabilize/capping in the nanoparticles’ fabrication process. Fourier Transform-Infrared, Scanning electron microscopy, Transmission Electron Microscopy, Energy dispersive X-Ray, X-ray powder diffraction and Thermogravimetric analysis (TGA) measurements were used to classify the as-synthesized nanoparticles. Moreover, we evaluated the antifungal mechanism of as-synthesized nanoparticles against different clinical isolates of C. auris. The minimum inhibitory concentrations and minimum fungicidal concentrations ranged from 0.39–0.78 μg/mL and 0.78–1.56 μg/mL. Cell count and viability assay further validated the fungicidal potential of Ag-Cu-Co trimetallic nanoparticles. The comprehensive analysis showed that these trimetallic nanoparticles could induce apoptosis and G2/M phase cell cycle arrest in C. auris. Furthermore, Ag-Cu-Co trimetallic nanoparticles exhibit enhanced antimicrobial properties compared to their monometallic counterparts attributed to the synergistic effect of Ag, Cu and Co present in the as-synthesized nanoparticles. Therefore, the present study suggests that the Ag-Cu-Co trimetallic nanoparticles hold the capacity to be a lead for antifungal drug development against C. auris infections.
Blinding, sham, and treatment effects in randomized controlled trials for back pain in 2000–2019: A review and meta-analytic approach

Background: Blinding aims to minimize biases from what participants and investigators know or believe. Randomized controlled trials, despite being the gold standard to evaluate treatment effect, do not generally assess the success of blinding. We investigated the extent of blinding in back pain trials and the associations between participant guesses and treatment effects. Methods: We did a review with PubMed/OvidMedline, 2000–2019. Eligibility criteria were back pain trials with data available on treatment effect and participants’ guess of treatment. For blinding, blinding index was used as chance-corrected measure of excessive correct guess (0 for random guess). For treatment effects, within- or between-arm effect sizes were used. Analyses of investigators’ guess/blinding or by treatment modality were performed exploratorily. Results: Forty trials (3899 participants) were included. Active and sham treatment groups had mean blinding index of 0.26 (95% confidence interval: 0.12, 0.41) and 0.01 (−0.11, 0.14), respectively, meaning 26% of participants in active treatment believed they received active treatment, whereas only 1% in sham believed they received sham treatment, beyond chance, that is, random guess. A greater belief of receiving active treatment was associated with a larger within-arm effect size in both arms, and ideal blinding (namely, “random guess,” and “wishful thinking” that signifies both groups believing they received active treatment) showed smaller effect sizes, with correlation of effect size and summary blinding indexes of 0.35 (p = 0.028) for between-arm comparison. We observed uniformly large sham treatment effects for all modalities, and larger correlation for investigator’s (un)blinding, 0.53 (p = 0.046). Conclusion: Participants in active treatments in back pain trials guessed treatment identity more correctly, while those in sham treatments tended to display successful blinding. Excessive correct guesses (that could reflect weaker blinding and/or noticeable effects) by participants and investigators demonstrated larger effect sizes. Blinding and sham treatment effects on back pain need due consideration in individual trials and meta-analyses.
Transmission-Blocking Vaccines: Harnessing Herd Immunity for Malaria Elimination

ABSTRACT Introduction Transmission-blocking vaccines (TBV) prevent community spread of malaria by targeting mosquito sexual stage parasites, a life-cycle bottleneck, and will be used in elimination programs. TBV rely on herd immunity to reduce mosquito infections and thereby new infections in both vaccine recipients and non-recipients, but do not provide protection once an individual receives an infectious mosquito bite which complicates clinical development. Areas covered Here, we describe the concept and biology behind TBV, and we provide an update on clinical development of the leading vaccine candidate antigens. Search terms ‘malaria vaccine,’ ‘sexual stages,’ ‘transmission blocking vaccine,’ ‘VIMT’ and ‘SSM-VIMT’ were used for PubMed queries to identify relevant literature. Expert opinion Candidates targeting P. falciparum zygote surface antigen Pfs25, and its P. vivax orthologue Pvs25, induced functional activity in humans that reduced mosquito infection in surrogate assays, but require increased durability to be useful in the field. Candidates targeting gamete surface antigens Pfs230 and Pfs48/45, respectively, are in or nearing clinical trials. Nanoparticle platforms and adjuvants are being explored to enhance immunogenicity. Efficacy trials require special considerations, such as cluster-randomized designs to measure herd immunity that reduces human and mosquito infection rates, while addressing human and mosquito movements as confounding factors.
Tumor metastasis has a significant relationship with the development of acute ischemic stroke in Chinese cancer patients: a retrospective study

Objective This study was designed to analyze the relationship between tumor metastasis and acute ischemic stroke (AIS) in Chinese cancer patients. Methods This retrospective study included 119 cancer patients with AIS and 152 cancer patients without AIS. Basic information was collected and tumor metastasis status was determined for all patients. Results The whole cohort had a median age of 59 (49–69) years with 150 men (55.4%). There were 98 patients (36.2%) with tumor metastasis. Patients with AIS had significantly more males, tumor metastasis, lung cancer, hypertension, diabetes mellitus, higher age, D-dimer, international normalized ratio, prothrombin time, prothrombin activity, and thrombin time, while they had significantly lower levels of hemoglobin, red blood cells, and hematocrit. In multivariate logistic regression analysis, AIS was significantly and positively associated with age, tumor metastasis, D-dimer, and thrombin time. In multivariate Cox regression analysis, tumor metastasis, AIS, D-dimer, thrombin time, and fibrinogen were significantly and positively associated with worse prognosis. Conclusions This study demonstrates that tumor metastasis was positively and independently associated with AIS in Chinese cancer patients, suggesting that tumor metastasis has a significant relationship with the development of AIS. Additionally, tumor metastasis and AIS had negative independent effects on the prognosis of patients.
Ramie Yield Estimation Based on UAV RGB Images

Timely and accurate crop growth monitoring and yield estimation are important for field management. The traditional sampling method used for estimation of ramie yield is destructive. Thus, this study proposed a new method for estimating ramie yield based on field phenotypic data obtained from unmanned aerial vehicle (UAV) images. A UAV platform carrying RGB cameras was employed to collect ramie canopy images during the whole growth period. The vegetation indices (VIs), plant number, and plant height were extracted from UAV-based images, and then, these data were incorporated to establish yield estimation model. Among all of the UAV-based image data, we found that the structure features (plant number and plant height) could better reflect the ramie yield than the spectral features, and in structure features, the plant number was found to be the most useful index to monitor the yield, with a correlation coefficient of 0.6. By fusing multiple characteristic parameters, the yield estimation model based on the multiple linear regression was obviously more accurate than the stepwise linear regression model, with a determination coefficient of 0.66 and a relative root mean square error of 1.592 kg. Our study reveals that it is feasible to monitor crop growth based on UAV images and that the fusion of phenotypic data can improve the accuracy of yield estimations.
Mucilages: sources, extraction methods, and characteristics for their use as encapsulation agents

Abstract The increasing interest in the use of natural ingredients has driven keen research and commercial interest in the use of mucilages for a range of applications. Typically, mucilages are polysaccharide hydrocolloids with distinct physicochemical and structural diversity, possessing characteristic functional and health benefits. Apart from their role as binding, thickening, stabilizing, and humidifying agents, they are valued for their antimicrobial, antihypertensive, antioxidant, antiasthmatic, hypoglycemic, and hypolipidemic activities. The focus of this review is to present the range of mucilages that have been explored as encapsulating agents. Encapsulation of food ingredients, nutraceutical, and pharmaceutical ingredients is an attractive technique to enhance the stability of targeted compounds, apart from providing benefits on delivery characteristics. The most widely adopted conventional and emerging extraction and purification methods are explained and supplemented with information on the key criteria involved in characterizing the physicochemical and functional properties of mucilages. The unique traits and benefits of using mucilages as encapsulation agents are detailed with the different methods used by researchers to encapsulate different food and bioactive compounds.
Insulin/IGF Axis in Breast Cancer: Clinical Evidence and Translational Insights

Background: Breast cancer (BC) is the most common neoplasm in women. Many clinical and preclinical studies investigated the possible relationship between host metabolism and BC. Significant differences among BC subtypes have been reported for glucose metabolism. Insulin can promote tumorigenesis through a direct effect on epithelial tissues or indirectly by affecting the levels of other modulators, such as the insulin-like growth factor (IGF) family of receptors, sex hormones, and adipokines. The potential anti-cancer activity of metformin is based on two principal effects: first, its capacity for lowering circulating insulin levels with indirect endocrine effects that may impact on tumor cell proliferation; second, its direct influence on many pro-cancer signaling pathways that are key drivers of BC aggressiveness. Methods: In the present review, the interaction between BC, host metabolism, and patients’ prognosis has been reviewed across available literature evidence. Conclusions: Obesity, metabolic syndrome, and insulin resistance are all involved in BC growth and could have a relevant impact on prognosis. All these factors act through a pro-inflammatory state, mediated by cytokines originated in fat tissue, and seem to be related to a higher risk of BC development and worse prognosis.
No Association Between SLC6A4 Gene Polymorphisms With Treatment Remission to Venlafaxine in Han Chinese Depressive Patients.

OBJECTIVE Major depressive disorder (MDD) is a heterogeneous psychiatric disorder and considered to be one of the most common mental diseases worldwide. The antidepressant venlafaxine, as a serotonin noradrenaline reuptake inhibitor, is applied to MDD relief. Solute carrier family 6 member 4 (SLC6A4) has been reported to promote the reuptake of serotonin and to be closely correlated to depression. The present study examined whether rs6354 and rs1487971 in SLC6A4 are associated with remission after venlafaxine treatment in MDD patients. METHODS This study consisted of 195 Han Chinese patients with MDD, who accepted a 6-week treatment with venlafaxine. Two SLC6A4 single-nucleotide polymorphisms (SNPs) were selected from database of SNP and genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometer in MassARRAY Analyzer 4 platforms. The 17-item Hamilton Depression Scale was used to access the severity of major depression. Allele and genotype frequencies between patients in remission and nonremission were calculated with online software SHEsis. RESULTS No significant differences in allele or genotype frequencies were observed in rs6354 and rs1487971. There were no significant associations between 2 SNPs and venlafaxine treatment outcome. CONCLUSIONS It suggested that rs6354 or rs1487971 within SLC6A4 appears not to be involved in the venlafaxine treatment outcome in Han Chinese patients with MDD.
Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.