Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of A-to-I microRNA editing with miRmedon reveals widespread co-editing of mature microRNA in the human brain

microRNA (miRNA), key regulators of gene expression, are prime targets for adenosine deaminase acting on RNA (ADAR) enzymes. Although ADAR-mediated adenosine-to-inosine (A-to-I) miRNA editing has been shown to be essential for orchestrating complex processes, including neurodevelopment and cancer progression, only few human miRNA editing sites have been reported. Several computational approaches have been developed for the detection of miRNA editing in small RNAseq data, all based on the identification of systematic mismatches of ‘G’ at primary adenosine sites in known miRNA sequences. However, these methods have several limitations, including their ability to detect only one editing site per sequence (although editing of multiple sites per miRNA has been reproducibly validated), their focus on uniquely mapping reads (even though 20% of human miRNA are transcribed from multiple loci), and their inability to detect editing in miRNA harboring genomic variants (though 73% of human miRNA loci include a reported SNP or indel). To overcome these limitations, we developed miRmedon, that leverages large-scale human variation data, a combination of local and global alignments, and a comparison of the inferred editing and error distributions, for confident detection of miRNA editing in small RNAseq data. We demonstrate the improved performance of miRmedon as compared to currently available methods and describe its advantages. We further use miRmedon to discover editing haplotypes of mature human brain miRNA for the first time. We find that doubly edited mature miRNA are common in the adult human prefrontal cortex, most include a frequently edited site within the miRNA seed region, and are predicted to maintain a stable pre-miRNA structure. These results suggest that co-editing of mature miRNA could enable efficient shifting of gene expression programs.
A DNA damage–induced phosphorylation circuit enhances Mec1ATR Ddc2ATRIP recruitment to Replication Protein A

The cell cycle checkpoint kinase Mec1ATR and its integral partner Ddc2ATRIP are vital for the DNA damage and replication stress response. Mec1-Ddc2 ‘senses’ single-stranded DNA (ssDNA) by being recruited to the ssDNA binding Replication Protein A (RPA) via Ddc2. In this study, we show that a DNA-damage induced phosphorylation circuit modulates checkpoint recruitment and function. We demonstrate that Ddc2-RPA interactions modulate the association between RPA and ssDNA and that Rfa1-phosphorylation aids in the further recruitment of Mec1-Ddc2. We also uncover an underappreciated role for Ddc2 phosphorylation that enhances its recruitment to RPA-ssDNA that is important for the DNA damage checkpoint in yeast. The crystal structure of a phosphorylated Ddc2 peptide in complex with its RPA interaction domain provides molecular details of how checkpoint recruitment is enhanced, which involves Zn2+. Using electron microscopy and structural modelling approaches, we propose that Mec1-Ddc2 complexes can form higher order assemblies with RPA when Ddc2 is phosphorylated. Together, our results provide insight into Mec1 recruitment and suggest that formation of supramolecular complexes of RPA and Mec1-Ddc2, modulated by phosphorylation, would allow for rapid clustering of damage foci to promote checkpoint signalling. Graphical Abstract Highlights Rfa1-S178 phosphorylation promotes Ddc2 recruitment and Ddc2-RPA complexes modulate RPA-ssDNA behaviour. Ddc2 phosphorylation enhances Mec1-Ddc2 recruitment and is important for the DNA damage checkpoint in yeast. Structure of a Ddc2:RPA complex shows phosphorylation-dependent higher order assemblies stabilised by Zn2+. We propose a Mec1-Ddc2 recruitment strategy that allows fast accumulation of Mec1-Ddc2 through DNA damage-induced phosphorylation and promotes autophosphorylation.
Biodiversity and Conservation Priority Setting for the Vascular Flora of New Guinea

Aims New Guinea is one of the world’s most floristically diverse islands, but its plant collection records are very uneven. We aim to identify which areas have the highest diversity of vascular plant genera, and which areas have the highest deforestation risk. Combining these findings we highlight priority regions for research and conservation. Location New Guinea Time period 1900–2021 Taxa studied Tracheophyta (Vascular plants) Methods We obtained collection records and environmental variables and prepared a cost-distance map of New Guinea to indicate accessibility. We modelled the joint distribution of 1,156 genera with the ‘Hmsc’ package in R to predict biodiversity across space, accounting for collection bias. We combined these results with a genus-level phylogenetic tree to predict phylogenetic endemism. We then modelled deforestation risk with the ‘R-INLA’ package, using forest clearance data and variables including cost-distance. We compared actual and predicted deforestation, and made predictions for 2021–25. Finally, we developed a combined measure of predicted biodiversity plus deforestation risk. Results A mean Spearman’s rank correlation of 0.462 was obtained on five-fold cross-validation of the genus biodiversity model; bias-correction shifted the predicted distribution of biodiversity towards western New Guinea, but had less effect on estimates of phylogenetic endemism. Predictions of relative deforestation probability were accurate over 5 and 10 years (Spearman values 0.66 and 0.71). We postulate a ‘deforestation debt’ to explain the persistence in accuracy. Over time, the areas which survive early deforestation gradually become more rewarding targets and the proportion of at-risk forest lost to clearance accumulates. Main conclusions We present a method for rapid assessment of biodiversity and deforestation risk in data-deficient tropical forest regions. Areas of high predicted biodiversity such as the Merauke and Jayapura lowlands are at high near-term risk from commercial deforestation, requiring urgent interventions to record and preserve threatened species.
Reach corrections toward moving objects are faster than reach corrections toward jumping targets

Visually guided reaching is a common motor behavior that engages subcortical circuits to mediate rapid corrections. These circuits help us successfully grasp objects we see, even if those objects move during the reach. Although these neural mechanisms have evolved for interaction with the physical world, they are almost always studied in the context of reaching toward virtual targets displayed on a computer or projection screen. Virtual targets are unrealistic both because they cannot be physically grasped and because they generally move by “jumping” from one place to another instantaneously. Recent work has indicated that various aspects of “real” visual stimuli, including proximity and graspability, elicit distinct neural activity. In this study, we instructed participants to perform rapid reaches to physical objects. On some trials, these objects either moved realistically (continuously from one position to another) or unrealistically (jumping instantaneously to an equivalent position). Participants were consistently faster in correcting their reach trajectories when the object moved continuously.
Asymptotic Analysis of Penalized Likelihood and Related Estimators

A general approach to the first order asymptotic analysis ofpenalized likelihood and related estimators is described. The method gives expansions for the systematic and random error. Asymptotic convergence rates in a family of spectral norms are obtained. The theory applies to a broad range of function estimation prob~erns including non"paxametric. dellSity, hazard and generalized regression curve estimation. Some examples are provided. AMS 1980 subject classifications. Primary, 62-G05, Secondary, 62J05, 41-A35, 41-A25, 47-A53, 45-LlO, 45-M05.
DEVELOPMENT OF METHOD AND VALIDATION FOR ASSAY IN IRINOTECAN HYDROCHLORIDE INJECTION BY APPLYING STABILITY INDICATING HPLC METHODOLOGY BY HPLC

A validated HPLC technique for determining Irinotecan Hydrochloride (IRN) in pharmaceutical formulations was developed. For this chromatographic investigation, isocratic elution at a flow rate of 1.0 ml/min was utilized on Zorbax C18 150mm 4.6 mm, 5μ, or similar. The mobile phase is made up of 45 volumes of methanol and 55 volumes of buffer solution. The UV detection wavelength was 220 nm, and a sample of 10.0 μl was injected. The run time for Sample, Unmarked, Placebo, System Suitability and Sensitivity solutions is approximately 12 minutes, and 60 minutes for diluted Regular. The approximate retention time for IRN was determined to be 3.8 minutes. The percentage R.S. D. IRN was determined. Irinotecan's mean percentage recovery is found to be within the specified limit. The approach was validated in accordance with ICH recommendations. As a result, the suggested HPLC approach may be successfully used for routine formulation quality control examination. The devised approach is simple and superior to the methods published in the literature.
Cycles and Propagation of Deep Convection over Equatorial Africa

AbstractLong-term statistics of organized convection are vital to improved understanding of the hydrologic cycle at various scales. Satellite observations are used to understand the timing, duration, and frequency of deep convection in equatorial Africa, a region with some of the most intense thunderstorms. Yet little has been published about the propagation characteristics of mesoscale convection in that region. Diurnal, subseasonal, and seasonal cycles of cold cloud (proxy for convective precipitation) are examined on a continental scale. Organized deep convection consists of coherent structures that are characteristic of systems propagating under a broad range of atmospheric conditions. Convection is triggered by heating of elevated terrain, sea/land breezes, and lake breezes. Coherent episodes of convection result from regeneration of convection through multiple diurnal cycles while propagating westward. They have an average 17.6-h duration and 673-km span; most have zonal phase speeds of 8–16 m s−1.P.
Complementary and alternative therapies for generalized anxiety disorder: A protocol for systematic review and network meta-analysis

Background: Generalized anxiety disorder (GAD) is a prevalent and impairing psychiatric disorder, which is a great threat to people’s mental health, and imposes a major burden on individuals, families and society. Complementary and alternative medicine (CAM) therapies is a potential treatment for GAD, however, the selection strategies of different CAM therapies in clinical practice is still unclear, and the purpose of this study is to evaluate the efficacy and acceptability of different CAM interventions using systematic review and network meta-analysis (NMA). Methods: Based on the strategy, the authors will retrieve a total of 9 electronic databases by January 2023. After a series of screening, the 2 researchers will use Aggregate Data Drug Information System (ADDIS) and Stata software to analyze the data extracted from randomized controlled trials (RCTs) of CAM therapies for the GAD. Finally, the evidence grade of the results will be evaluated. Results: This study will provide a reliable evidence for the selection of CAM therapies for GAD. Conclusion: The results of this study will provide references for evaluating the influence of different CAM therapies for GAD, and provide a choice basis for clinical decision-making.
Higher TYROBP and lower SOX6 as predictive biomarkers for poor prognosis of clear cell renal cell carcinoma: A pilot study

Background: Clear cell renal carcinoma (ccRCC) is the most common subtype of renal cancer, accounting for approximately 75% of all histological types of renal cancer, and is the leading cause of death from renal cancer. However, the molecular mechanism of tyrosine kinase binding protein (TYROBP) and sex-determining region Y Box-6 (SOX6) in the ccRCC was not precise. Methods: Bioinformatics analysis was performed to explore the hub role of TYROBP and SOX6 on the ccRCC. A total of 6 patients with clear cell renal cell carcinoma (ccRCC) were recruited. HE staining was performed to observe the pathology result of ccRCC. Immunohistochemistry and Immunofluorescence assay was made to detect the protein expression of TYROBP. Total RNA was extracted using TRIzol to examine the mRNA expression of TYROBP via the Real time quantitative polymerase chain reaction. The strong correlation between the expression of TYROBP and the survival time of ccRCC patients was performed by the BP neural network and support vector machine. Results: Compared with the control group, the expression of SOX6 was downregulated in the samples with ccRCC. However, the expression of TYROBP was higher in the samples with ccRCC than in the control group. Compared with the patients with high SOX6 expression, the patients with low SOX6 expression have a poor survival prognosis (HR=0.39, P < .05). However, the patients with high TYROBP expression have a shorter survival time than the patients with low TYROBP expression (HR=1.66, P < .05). The genes related with TYROBP and SOX6 are mainly enriched in the regulation of cell activation, leukocyte activation, negative regulation of cell activation, myeloid leukocyte activation, positive regulation of response to external stimulus, immune response-regulating signaling pathway. The interaction between TYROBP, SOX6, and kidney neoplasms was drawn, and the inference score of TYROBP and SOX6 on the kidney neoplasms was high. Conclusion: In conclusion, TYROBP is highly expressed in renal clear cell carcinoma, and when this molecule is highly expressed, the survival prognosis of renal carcinoma is poor. TYROBP and SOX6 may be potential targets for diagnosing and treating renal clear cell carcinoma.
Reconstruction of three-dimensional conductivity variations from eddy current (electromagnetic induction) data

A direct linear inverse method for eddy current nondestructive evaluation is presented. The method is based on inverting the impedance change measured in an eddy current probe, placed above a conducting half-space containing a three-dimensional (3D) conductivity anomaly. The eddy current probe used for this purpose consists of a spatially periodic, time-harmonic current sheet. The Born approximation is used to linearize the relevant integral equations used for inversion. It is found that a coupled Fourier-Laplace transform has to be inverted to provide a 3D reconstruction of the inhomogeneity in the conventional frequency domain; however, the transforms decouple in the time domain.
Effect of projection number on slice image quality of micro-CT system

The number of projection affects the reconstruction quality in computed tomography system. Larger projection number will lead to better reconstruction quality. Infinite projections can reconstruct the specimen without mathematical error. On the other hand, less projection number can reduce the radiation dose, save time and keep the patients comfortable. The optimal number of projection compromises both the mathematical accuracy and real-life requirement. The purpose of this paper is to find the relationship between the projection number and the reconstruction quality. A micro-CT system is developed to validate the relationship between projection number and reconstruction quality. But the actual precision and signal to noise ratio is hard to find in experiments, because the sample are not standard whose physical characteristics are certain. We can only provide limited projection number and get relative reconstruction quality in the experiment. Half-scan method can reduce radiation dose, and it can achieve better results with sufficient sampling.
Efficacy and safety of single- and multiple-antenna microwave ablation for the treatment of hepatocellular carcinoma and liver metastases: A systematic review and network meta-analysis

Background: There is a myriad of microwave ablation (MWA) systems used in clinical settings worldwide for the management of liver cancer that offer a variety of features and capabilities. However, an analysis on which features and capabilities result in the most favorable efficacy and safety results has never been completed due to a lack of head-to-head comparisons. The aim of this study is to compare single-antenna and multiple-antenna MWA using radiofrequency ablation (RFA) as a common comparator in the treatment of very-early, early hepatocellular carcinoma (HCC) and ≤5 cm liver metastases. Methods: This network meta-analysis was performed according to PRISMA guidelines. PubMed, Cochrane, and Web of Science databases were searched for comparative studies. Complete ablation (CA) rate, local tumor progression-free (LTPF) rate, overall survival (OS), and major complication rate were assessed. Subgroup analyses were further performed based on synchronous or asynchronous MWA generators and tumor size (<2 cm or ≥2 cm). Results: Twenty-one studies (3424 patients), including 3 randomized controlled trials (RCTs) and 18 observational studies, met eligibility criteria. For CA, LTPF and major complications, as compared to single-antenna MWA, multiple-antenna MWA had relative risks (RRs) of 1.051 (95% CI: 0.987–1.138), 1.099 (95% CI: 0.991–1.246), and 0.605 (95% CI: 0.193–1.628), respectively. For 1-year and 3-year OS, as compared to single-antenna MWA, multiple-antenna MWA had odds ratios (ORs) of 0.9803 (95% CI: 0.6772–1.449) and 1.046 (95% CI: 0.615–1.851), respectively. Subgroup analysis found synchronized multi-antenna MWA was associated with significantly better LTPF by 22% (RR: 1.22, 95% CI 1.068, 1.421), and 21.4% (RR: 1.214, 95% CI 1.035, 1.449) compared with single-antenna MWA, and asynchronous multiple-antenna MWA, respectively, with more evident differences in larger tumors (≥2 cm). Conclusion: Multi-antenna and single-antenna MWA showed similar effectiveness for local treatment of liver tumors, but synchronous multi-antenna MWA exhibited better LTPF compared to other MWA approaches, particularly for larger liver tumors (≥2 cm). Large-scale RCTs should be further conducted.
Efficacy of Csaba stain to demonstrate mature and immature mast cells in oral inflammatory lesions: An in-vitro study

Background: Mast cells (MCs) are immune cells of the myeloid lineage and are present in connective tissues throughout the body. Mastocytosis regulates many physiologic processes and affects the pathogenesis of allergic conditions, anaphylactic reactions, autoimmune disorders and leukemias. Toluidine blue is commonly employed as a special stain for MCs that uniformly imparts blue color to both immature and mature cells. Csaba stain that distinguishes mature from immature MCs has not been widely explored. However, its use in differentiating mature and immature cells has not been reported in the literature. The identification of mature and immature MCs may provide a major clue for the diagnosis of any unrecognized systemic pathologies. Objectives: To evaluate the staining efficacy of Csaba stain, toluidine blue and Leishman's stains in the identification of MCs To compare the effectiveness of Csaba stain, toluidine blue and Leishman's stains to identify MCs in inflammatory pathologic lesions. Materials and Methods: Fifty sections of inflammatory lesions were subjected to Csaba stain, toluidine blue and Leishman's stains each for studying MCs. The staining efficacy of the three stains was compared for parameters such as homogeneity, specificity, staining intensity, granular staining property and differentiation between mature and immature cells. Results: The Csaba, toluidine blue and Leishman's stains showed statistically insignificant P = 0.50, 0.95, 0.29, 0.48 for homogeneity, specificity, staining intensity and granular staining property respectively, but Csaba stain showed statistically significant P = 0.0001* in differentiating mature from immature cells. Conclusion: Csaba stain is more effective in differentiating mature from immature MCs compared to the other special stains.
The changes that occur in the immune system during immune activation in pre-diabetic patients of all ethnicities, from the age of 25- to 45-years: A systematic review and meta-analysis

Background: Pre-diabetes is an intermediate state between normoglycaemia and type 2 diabetes (T2D). This condition has been shown to be asymptomatic thus making it hard to investigate the changes that occur in the body during this state. Recent findings stipulate that in this state, there are changes that are often associated with T2D. These include changes in concentration of immune cells and inflammatory markers. This systematic review will provide a synthesis of the data that is available reporting on the changes in the concentration of immune cells and selected markers during prediabetes. It will also give clarity of the variation of the complications of the condition among the various demographic groups. Methods: The assembly of this systematic review was through strict adherance to the PRISMA 2020 guidelines for reporting systematic reviews. This systematic review has been registered with the International Prospective Registry of Systematic Reviews (PROSPERO), registration number “CRD42020184828” dated 05-07-2020). In this systematic review, published clinical studies articles that involve observational reports, whether it is case-control, cross-sectional, and comparative cross-sectional will be used. Cohort study designs that involve normal/non-diabetic and pre-diabetes reports will be used in this systematic review and meta-analysis. Clinical MeSH headings to search on MEDLINE, COCHRANE library, EMBASE, and ICTRP and African Journal Online will be a tool used to achieve the required report. Reviewers (NCM, AMS, and AK) will screen all the results and select the studies that will be eligible by guidance according to eligibility criteria. Downs and Black Checklist will be used to check the risk of bias and then for meta-analysis Review Manager v5.4 Forrest plot will be used. Additionally, the Forrest plot will also be used for sensitivity analysis. The strength of evidence will then be assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Only 4 reports were eligible and risk of bias checked. The results indicated the outcomes even though there were only few reports. Discussion and conclusion: This systematic review will give an indication on the available data on this research area and lay a foundation for future studies.